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Ka whakaitihia e ngā granules Ban-Lan-Gen te colitis mau tonu i puta mai i te dextran sodium sulfate i roto i ngā kiore mā te whakarerekē i ngā microbiota puku me te whakaora i te hanga SCFA Derived-GLP-1 o te puku.
Jiao Peng,1-3,*Li Xi,4,*Zheng Lin,3,5 Duan Lifang,1 Gao Zhengxian,2,5 Diehu,1 Li Jie,6 Li Xiaofeng,6 Shen Xiangchun,5 Xiao Haitao21Te Whare Wānanga o Peking Tari Rongoā o Shenzhen Hōhipera, Shenzhen, te Repupiripia o Haina;2Te Pokapū Pūtaiao Hauora o te Whare Wānanga o Shenzhen Kura Rongoā, Shenzhen, te Repupiripia o Haina;3Te Whare Wānanga Hauora o Guizhou Te Pokapū Rangahau Hangarau Hangarau mō te Rongoā Iwi me te Rongoā Hainamana Tuku Iho Te Manatū Mātauranga, Te Taiwhanga Matua o te Rohe o Guizhou mō te Rongoā, Te Whare Wānanga Hauora o Guizhou, Guiyang, te Repupiripia o Haina;4Te Tari Gastroenterology, Te Whare Wānanga o Peking Hōhipera o Shenzhen, Shenzhen, te Repupiripia o Haina;5Te Kura Rongoā, Te Whare Wānanga Hauora o Guizhou, Te Taiwhanga Matua o te Kāwanatanga mō te Mahi me te Tono o ngā Tipu Rongoā, Guiyang; 6 Tari Rongoā Taiwhanga, Whare Wānanga o Peking Hōhipera Shenzhen, Shenzhen, Haina [email protected] Shen Xiangchun, Kura Rongoā, Whare Wānanga Hauora o Guizhou, Guizhou, Repupiripia o te Iwi o Haina, 550004, Īmēra [email protected] Whāinga: Ko te rongoā e hangai ana ki te GLP-1 he kōwhiringa maimoatanga hou mō te mate puku mumura. Ko ngā paura Ban-Lan-Gen (BLG) he hanganga TCM ārai huaketo e mōhiotia ana e whakaatu ana i te kaha anti-inflammatory i roto i te maimoatanga o ngā momo mate mumura. Heoi, kāore anō kia mārama tōna pānga anti-inflammatory ki te colitis me tōna tikanga mahi. NGĀ TIKANGA: Hei whakatū i te colitis relapsing mau tonu i puta mai i te dextran sodium sulfate (DSS) i roto i ngā kiore. I mahia ngā tohu mahi mate, ngā tohu histological o te whara, me ngā taumata cytokine proinflammatory hei aromatawai i te pānga tiaki o te BLG. Ko ngā pānga o te BLG ki te microbiota puku me te puku i whakaahuatia e ngā taumata GLP-1 serum me te colonic Gcg, GPR41, me te whakaaturanga GRP43, te hanganga microbiota puku, ngā taumata SCFA paru, me Te tukunga GLP-1 mai i ngā pūtau epithelial koroni tuatahi o te kiore te hanga GLP-1 i ahu mai i te SCFA. Ngā Hua: Nā te maimoatanga BLG i whakaiti nui i te ngaronga taumaha o te tinana, te DAI, te whakapoto o te koroni, te kino o te kiko koroni, me ngā taumata cytokine mumura o te TNF-α, IL-1β, me te IL-6 i roto i te kiko koroni. Hei tāpiri, ka taea e te maimoatanga BLG te whakaora nui i te whakaaturanga Gcg koroni, GPR41 me te GRP43 me ngā taumata GLP-1 serum i roto i ngā kiore colitis, me te whakanui ake i ngā huakita whakaputa SCFA pēnei i a Akkermansia me Prevotellaceae_UCG-001, me te whakaiti i te nui o ngā huakita pēnei i a Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas me Oscillibacter. Hei tāpiri, ka taea e te maimoatanga BLG te whakanui ake i te taumata o ngā SCFA i roto i ngā paru o ngā kiore colitis. I taua wā anō, i whakaatuhia hoki e ngā whakamātautau in vitro ka taea e te tango paru o ngā kiore i rongoatia ki te BLG te whakaoho nui i ngā pūtau epithelial koroni Murine iti tuatahi e huna ana i te GLP-1. Ngā Whakatau: E whakaatu ana ēnei kitenga he pānga ārai-koripi te BLG. Kei a BLG te kaha ki te whakawhanake hei rongoā, mā te whakarerekē i ngā moroiti puku me te whakaora i te hanga GLP-1 i ahu mai i te SCFA. He rongoā whai hua mō te koripi e hokihoki tonu ana. Ngā Kupumatua: koripi, ngā paura Ban-Lan-Gen, ngā moroiti puku, ngā waikawa ngako mekameka-poto, GLP-1.
Ko te mate puku puku (UC) he mate mumura roa o te koroni me te rectum e tohuhia ana e te mate korere auau, te mamae o te puku, te whakaheke taumaha, me ngā tūtae toto mucopurulent.1 Nō nā tata nei, kua piki haere te horapa o te UC i ngā whenua iti te mate i mua, tae atu ki Haina, me te piki haere o te rongonui o ngā momo noho o te Hauāuru.2 He raruraru nui tēnei mō te hauora o te iwi whānui, ā, he pānga nui ki te kaha o ngā tūroro ki te mahi me te kounga o te oranga. He mea nui, kāore i te mārama te pathogenesis o te UC, engari e whakaaetia whānuitia ana ko ngā ira, ngā āhuatanga taiao, te microbiota puku, me te pūnaha ārai mate katoa e whai wāhi ana ki te whanaketanga o te UC.3 Ahakoa i nāianei, kāore he rongoā mō te UC, ā, ko te whāinga o te maimoatanga he whakahaere haumanu i ngā tohu haumanu, te whakaoho me te pupuri i te murunga, te whakatairanga i te whakaora mucosal, me te whakaiti i te hokinga mai. Ko ngā maimoatanga tawhito ko te aminosalicylates, corticosteroids, immunosuppressants, me ngā biologics. Heoi, kāore e taea e ēnei rongoā te whakatutuki i te pānga e hiahiatia ana nā ō rātou pānga taha.4 Nō nā tata nei, he maha ngā rangahau take kua whakaatu kua whakaatuhia e te rongoā tuku iho Hainamana (TCM) te kaha nui ki te āwhina i te whakaora i te UC me te iti o te paitini, e kī ana he rautaki maimoatanga whai hua te whanaketanga o ngā maimoatanga TCM hou mō UC.5-7
Ko ngā Banlangen Granules (BLG) he rongoā tuku iho Hainamana i hangaia mai i te tango wai o te pakiaka Banlangen.8 Haunga tōna whai huatanga ārai huaketo, he kaha te mahi ārai-mumura a te BLG ki te rongoā i ngā momo mate mumura.9,10 Hei tāpiri, kua wehea, kua tautuhia hoki ngā glucosinolates (R,S-goitrin, progoitrin, epiprorubin me te glucoside mai i ngā tango wai o Radix isatidis) me ngā nucleosides (hypoxanthine, adenosine, uridine me te guanosine) me ngā indigo alkaloids pērā i te indigo me te indirubin.11,12 Kua tuhia pai e ngā rangahau o mua ko ngā matū adenosine, uridine me te indirubin he kaha ki te ārai i te colitis i roto i ngā tauira kararehe rerekē o te colitis.13-17 Heoi, kāore anō kia mahia he rangahau e ahu mai ana i ngā taunakitanga hei aromatawai i te whai huatanga o te BLG i roto i te colitis. I roto i tēnei rangahau, i tirotirohia e mātou te pānga tiaki o te BLG ki te colitis relapsing mau tonu i puta mai i te dextran sodium sulfate (DSS) i roto i ngā kiore C57BL/6, ā, i kitea ko te whakahaerenga ā-waha o te BLG i tino whakaiti i te mumura o te kōpuku e hoki whakamuri ana i roto i ngā kiore nā te DSS, ā, ko ōna tikanga whakahaere e pā ana ki te whakarerekētanga o ngā microbiota o te puku me te whakahokinga mai o te hanga glucagon-like peptide-1 (GLP-1) i ahu mai i te puku.
I hokona ngā kirikiri BLG (kāore he huka, kua whakaaetia e te NMPA Z11020357; Beijing Tongrentang Technology Development Co., Ltd., Beijing, Haina; tau puranga: 20110966) mai i ngā whare rongoā. I hokona te DSS (Taumaha Ngota: 36,000–50,000 Daltons) mai i MP Biologicals (Santa Ana, USA). I ​​hokona te Sulfasalazine (SASP) (≥ 98% parakore), te hematoxylin me te eosin mai i Sigma-Aldrich (St. Louis, MO, USA). I ​​hokona ngā kete whakamātautau kiore TNF-α, IL-1β me te IL-6 luminex Elisa mai i ngā pūnaha R&D (Minneapolis, MN, USA). I ​​hokona te waikawa acetic, te waikawa propionic, me te waikawa butyric mai i Aladdin Industries (Shanghai, Haina). I hokona te waikawa 2-Ethylbutyric mai i Merck KGaA (Darmstadt, Tiamana).
I hokona mai ngā kiore tāne C57BL/6, 6-8-wiki te pakeke (te taumaha tinana 18-22 g) mai i Beijing Wetahe Laboratory Animal Technology Co., Ltd. (Beijing, Haina) ā, i whakanohoia ki roto i te taiao 22 ± 2 °C me te huringa mārama/pōuri 12 h. I whāngaihia ngā kiore ki te kai noa mō ngā kiore me te urunga kore utu ki te wai inu mō te wiki kotahi hei taunga ki te taiao hou. Kātahi ka wehea matapōkeretia ngā kiore ki ngā rōpū e whā: te rōpū whakahaere, te rōpū tauira DSS, te rōpū i rongoatia ki te SASP (200 mg/kg, ā-waha) me te rōpū i rongoatia ki te BLG (1 g/kg, ā-waha). E ai ki te Pikitia 1A, e ai ki tā mātou rangahau o mua, i whakaohokia te mate puku whakamuri mau tonu i roto i ngā kiore e toru ngā huringa o te 1.8% DSS mō ngā rā e 5, ā, i muri mai ko te wai whakamātao mō ngā rā e 7, e ai ki tā mātou rangahau o mua.18 Ko ngā kiore i roto i ngā rōpū i rongoatia ki te SASP me te BLG i rongoatia ki te SASP me te BLG, ia rā, mai i te rā 0. E ai ki ngā whakamātautau tuatahi, ko te I whakatakotoria te horopeta o te BLG ki te 1 g/kg. I taua wā, i whakatakotoria te horopeta o te SASP ki te 200 mg/Kg e ai ki ngā tuhinga.4 I whiwhi te rōpū mana whakahaere me te rōpū tauira DSS i te nui o te wai ōrite puta noa i te whakamātautau.
Pikitia 1 Ka whakapai ake te BLG i te mate puku pūmau i puta mai i te DSS i roto i ngā kiore. (A) Hoahoa whakamātautau o te mate puku pūmau me te maimoatanga, (B) huringa taumaha tinana, (C) kaute taupū ngohe mate (DAI), (D) roa o te koroni, (E) ahua tohu o te koroni, (F) tae H&E Koroni (whakanui, ×100) me te (G) kaute histological. Ka whakaatuhia ngā raraunga hei toharite ± SEM (n = 6).##p < 0.01 ###p < 0.001 rānei vs rōpū mana (Con); *p < 0.05 **p < 0.01 rānei ***p < 0.001 rānei vs rōpū DSS.
I tuhia ia rā te taumaha o te tinana, te ōritetanga o te tūtae, me te toto o te pūwero. I whakatauhia te taupū ngohe mate (DAI) mā te whakakotahi i ngā kaute o te taumaha o te tinana, te ōritetanga o te tūtae, me te toto o te pūwero e ai ki te whakaahuatanga o mua.19 I te mutunga o te whakamātautau, i whakamatea ngā kiore katoa, ā, i kohia te toto, te tūtae me te puku mō ētahi atu whakamātautau.
I whakapūmauhia te kiko koroni ki te formalin, ā, i whakatōkia ki roto i te paraffin. I hangaia ngā wāhanga 5-micron, ā, i pania ki te hematoxylin-eosin (H&E), kātahi ka matapohia, ka tohua kia rite ki te whakaahuatanga o mua.19
I tangohia te RNA katoa o te kiko koroni mā te whakamahi i te matū Trizol (Invitrogen, Carlsbad, CA), ā, i muri mai ka tangohia te cDNA mā te whakamahi i te transcriptase whakamuri (TaKaRa, Kusatsu, Shiga, Hapani). I mahia te PCR tauanga mā te whakamahi i te pūnaha PCR wā-tūturu me te SYBR Green Master (Roche, Basel, Switzerland). I whakatauritea ngā tuhinga ira ūnga ki te β-actin, ā, i tātarihia ngā raraunga mā te whakamahi i te tikanga 2-ΔΔCT. Kei te whakaatuhia ngā raupapatanga ira tuatahi i te Ripanga 1.
I mahia te wehenga me te ahurea o ngā pūtau epithelial koroni tuatahi o te kiore e ai ki te whakaahuatanga o mua.20 I te poto, i tangohia tuatahitia ngā koroni o ngā kiore 6-8 wiki te pakeke i muri i te patunga mā te wehenga o te kaki, kātahi ka whakatuwheratia te taha roa, ka rongoatia ki te Hanks Balanced Salt Solution (HBSS, kāore he konupūmā me te konupora) ā, ka tapahia kia 0.5-1 mm o ngā wahi iti. Muri iho, i keria ngā kiko ki te 0.4 mg/mL collagenase XI (Sigma, Poole, UK) i roto i te reo DMEM kore utu, ā, i whakatōngia ki te 300 xg mō te 5 meneti i te pāmahana rūma. Whakatārewatia anō te pire ki roto i te reo DMEM (i tāpirihia ki te 10% fetal bovine serum, 100 Units/mL penicillin, me te 100 µg/mL streptomycin) i te 37 °C, ā, ka tukuna mā roto i te mata nairona (rahi o te pore ~250 µm). I whakanohoia ngā wāhanga o ngā pūtau epithelial koroni ki roto i ngā rihi raro-karaihe, ā, i whakatōkia ki te waikawa acetic, te waikawa propionic, te waikawa butyric, me te paru kiore. tangohanga mō ngā hāora e 2 i te 37°C, 5% CO2.
I whakakotahihia te kiko koroni ki te PBS, ā, i kitea ngā taumata o ngā cytokine IL-6, TNF-α me te IL-1β i roto i te kiko koroni mā te whakamahi i ngā kete whakamātautau luminex ELISA (ngā pūnaha R&D, Minneapolis, MN, USA). Waihoki, i whakatauhia ngā taumata GLP-1 i roto i te serum me te reo ahurea o ngā pūtau epithelial koroni kiore tuatahi mā te whakamahi i te kete ELISA (Bioswamp, Wuhan, Haina) e ai ki ngā tohutohu a te kaihanga.
I tangohia te DNA katoa mai i ngā paru mā te whakamahi i tētahi kete tango DNA (Tiangen, Haina). I inehia te kounga me te rahinga o te DNA i ngā ōwehenga o te 260 nm/280 nm me te 260 nm/230 nm. I muri mai, mā te whakamahi i ia DNA i tangohia hei tauira, i whakamahia ngā paraimere motuhake 338F (ACTCCTACGGGAGGCAGCAG) me te 806R (GGACTACHVGGGTWTCTAAT) hei whakanui ake i ngā rohe V3-V4 o te ira 16S rRNA i ngā rohe rerekē. I purea ngā hua PCR mā te whakamahi i te QIAquick Gel Extraction Kit (QIAGEN, Tiamana), i inehia mā te PCR wā-tūturu, ā, i raupapahia mā te whakamahi i te tūāpapa raupapatanga IlluminaMiseq PE300 (Illumina Inc., CA, USA). Mō te tātaritanga bioinformatics, i mahia te tukatuka raraunga i muri i ngā kawa i pūrongohia i mua.21,22 I roto i te poto, whakamahia a Cutadapt (V1.9.1) hei tātari i ngā kōnae tere mata. I whakarōpūhia ngā OTU mā te whakamahi i te UPARSE (putanga 7.0.1001) me te tapahi ōrite o te 97%, ā, i whakamahia a UCHIME hei tango i ngā raupapatanga chimeric. I whakahaerehia te tātaritanga hanganga hapori me te whakarōpūtanga mā te whakamahi i te kaiwhakarōpū RDP (http://rdp.cme.msu.edu/) i runga i te pātengi raraunga ira RNA ribosomal SILVA.
I inehia ngā taumata o ngā waikawa ngako mekameka-poto (waikawa acetic, waikawa propionic, me te waikawa butyric) e ai ki tā Tao et al. i whakaahua i mua, me ētahi whakarerekētanga.23 I roto i te poto, i tuatahitia te 100 mg o ngā paru i roto i te 0.4 mL o te wai whakakore iona, ā, i muri mai ko te 0.1 mL o te 50% waikawa whanariki me te 0.5 mL o te waikawa 2-ethylbutyric (paerewa ā-roto), kātahi ka whakaranua, ka whakamahanatia ki te 4°C. I whakapūtāhia i te 12,000 rpm mō te 15 meneti i te C. I tangohia te wai i roto i te wai me te 0.5 mL o te ether, ā, i werohia ki roto i te GC hei tātari. Mō te tātari hau chromatography (GC), i tātarihia ngā tauira mā te whakamahi i te chromatography hau GC-2010 Plus (Shimadzu, Inc.) me te taputapu kite ionization mura (FID). I tutuki te wehenga mā te whakamahi i te pou ZKAT-624, 30 m × 0.53 mm × 0.3 μm (Lanzhou Zhongke Antai Analytical Technology Co., Ltd., Haina). I kohia ngā raraunga mā te whakamahi i te pūmanawa otinga GC (Shimadzu, Inc.). Ko te ōwehenga wehenga he 10:1, ko te hau kawe he hauota, ā, ko te tere rere he 6 mL/min. Ko te rōrahi werohanga he 1 μL. Ko te pāmahana o te werohanga me te taputapu kite he 300°C. I puritia te pāmahana oumu ki te 140°C mō te 13.5 meneti, kātahi ka whakanuia ki te 250°C i te tere o 120°C/min; i puritia te pāmahana mō te 5 meneti.
Ka whakaatuhia ngā raraunga hei toharite ± hapa paerewa o te toharite (SEM). I aromatawaihia te hiranga o ngā raraunga mā te ANOVA kotahi-ara, ā, i whai muri ko te whakamātautau whānuitanga maha a Duncan. I whakamahia te pūmanawa GraphPad Prism 5.0 (GraphPad Software Inc., San Diego, CA, USA) mō ngā tataunga katoa, ā, i kiia ko te p < 0.05 he hiranga tatauranga.
E mōhiotia whānuitia ana ko te UC he mate puku roa e hoki whakamuri ana me te mamae nui o te puku, te korere me te toto. Nō reira, i whakatūria te DSS-induced chronic relapsing colitis i roto i ngā kiore hei aromatawai i te whai huatanga o te BLG anti-colitis (Pikitia 1A). Ki te whakatauritea ki te rōpū whakahaere, he nui te hekenga o te taumaha tinana o ngā kiore i roto i te rōpū tauira DSS me te DAI teitei ake, ā, i tino hurihia ēnei huringa i muri i ngā rā 24 o te maimoatanga BLG (Pikitia 1B me C). Ko te whakapoto koroni he tohu nui o te UC. E ai ki ngā Pikitia 1D me E, i tino whakapotohia te roa o te koroni o ngā kiore i whiwhi DSS, engari i whakaorangia e te maimoatanga BLG. Muri iho, i mahia te tātaritanga histopathological hei aromatawai i te mumura koroni. I whakaatuhia e ngā whakaahua H&E me ngā kaute pathological ko te whakahaeretanga DSS i tino whakararuraru i te hanganga koroni, ā, i hua ake ai te whakangaromanga o te crypt, engari ko te maimoatanga BLG i tino whakaiti i te whakangaromanga o te crypt me ngā kaute pathological (Pikitia 1F me G). He mea nui, ko te pānga tiaki o te BLG i te horopeta o te 1 g/Kg he rite ki te SASP i he horopeta o te 200 mg/Kg. E whakaatu tahi ana ēnei kitenga he whai hua te BLG ki te whakaiti i te kaha o te mate puku hoha mau tonu i puta mai i te DSS i roto i ngā kiore.
He tohu mumura nui ngā TNF-α, IL-1β me te IL-6 mō te mumura o te koroni. E ai ki te Whakaahua 2A, i puta he pikinga nui o te whakaaturanga ira o te TNF-α, IL-1β me te IL-6 i roto i te koroni i te DSS ki te whakataurite ki te rōpū whakahaere. Mā te whakahaere i te BLG ka taea te whakakore i ēnei huringa e whakahaerehia ana e te DSS. Muri iho, i whakamahia e mātou te ELISA hei whakatau i ngā taumata o ngā cytokine mumura TNF-α, IL-1β, me te IL-6 i roto i te kiko koroni. I whakaatuhia hoki e ngā hua he nui te pikinga o ngā taumata koroni o te TNF-α, IL-1β, me te IL-6 i roto i ngā kiore i rongoatia ki te DSS, engari i whakaitihia e te maimoatanga BLG ēnei pikinga (Whakaahua 2B).
Ahua 2 Ka aukati te BLG i te whakaaturanga ira me te whakaputanga o ngā cytokine mumura TNF-α, IL-1β me te IL-6 i roto i te koroni o ngā kiore i rongoatia ki te DSS.(A) Te whakaaturanga ira koroni o te TNF-α, IL-1β me te IL-6; (B) ngā taumata pūmua koroni o te TNF-α, IL-1β me te IL-6. Ka whakaatuhia ngā raraunga hei toharite ± SEM (n = 4–6).#p < 0.05 ##p < 0.01 rānei ###p < 0.001 vs rōpū mana (Con); *p < 0.05 **p < 0.01 vs rōpū DSS rānei.
He mea nui te dysbiosis puku i roto i te pathogenesis o te UC.24 Hei tirotiro mēnā ka whakarerekē te BLG i te microbiota puku o ngā kiore i rongoatia ki te DSS, i whakahaerehia te raupapatanga 16S rRNA hei tātari i te hapori huakita o ngā ihirangi puku. E whakaatu ana te tūtohi Venn e 385 ngā OTU e tohaina ana e ngā rōpū e toru. I taua wā anō, he OTU ahurei tō ia rōpū (Pikitia 3A). I ​​tua atu, ko te tohu Chao1 me te tohu Shannon e whakaaturia ana i te Pikitia 3B me te C i whakaatu i te hekenga o te kanorau hapori o te microbiota puku i roto i ngā kiore i rongoatia ki te BLG, i te mea kua heke te tohu Shannon i roto i te rōpū i rongoatia ki te BLG. I whakamahia te tātaritanga wāhanga matua (PCA) me te tātaritanga taunga matua (PCoA) hei whakatau i ngā tauira rōpū i waenga i ngā rōpū e toru, ā, i whakaatu i te wehewehenga mārama o te hanganga hapori o ngā kiore i rongoatia ki te DSS i muri i te maimoatanga BLG (Pikitia 3D me te E). E kī ana ēnei raraunga he nui te pānga o te maimoatanga BLG ki te hanganga hapori o ngā kiore me te colitis i puta mai i te DSS.
Ahua 3 Ka whakarerekē te BLG i te kanorau o ngā microbiota puku i roto i ngā kiore me te colitis i puta mai i te DSS. (A) Te tūtohi Venn o OTU, (B) Te taupū Chao1, (C) Te taupū momona a Shannon, (D) Te kauwhata kaute Tātari Wāhanga Matua (PCA) o OTU, (E) Te kaute Tātari Taurite Matua OTU (PCoA) Ahua. Ka whakaatuhia ngā raraunga hei toharite ± SEM (n = 6).**p < 0.01 vs rōpū DSS.
Hei aromatawai i ngā huringa motuhake o ngā microbiota paru, i tātarihia e mātou te hanganga o ngā microbiota puku i ngā taumata whakarōpū katoa. E ai ki te Whakaahua 4A, ko ngā phyla matua i roto i ngā rōpū katoa ko Firmicutes me Bacteroidetes, ā, i muri mai ko Verrucomicrobia. Ko te nui o ngā ōwehenga Firmicutes me Firmicutes/Bacteroidetes i tino piki ake i roto i ngā hapori microbial paru o ngā kiore i rongoatia ki te DSS ki te whakataurite ki ngā kiore mana, ā, i tino hurihia ēnei huringa i muri i te maimoatanga BLG. Ina koa, i tino whakanuia e te maimoatanga BLG te nui o Verrucobacterium i roto i ngā paru o ngā kiore me te colitis i puta mai i te DSS. I te taumata whare, i nohoia ngā hapori microbial paru e Lachnospiriaceae, Muribaculaceae, Akkermansiaceae, Ruminococcaceae me Prevotellaceae (Pikitia 4B). Ki te whakataurite ki te rōpū DSS, ko te hekenga o te BLG i whakanui ake i te nui o Akkermansiaceae, engari i whakaitihia te nui o Lachnospiraceae me Ruminococcaceae. He mea nui, i te puninga taumata, i nohoia ngā moroiti paru e te rōpū Lachnospira_NK4A136, Akkermansia me Prevotellaceae_UCG-001 (Pikitia 4C). I whakaatuhia hoki e tēnei kitenga he pai te whakakorenga o te maimoatanga BLG i te kore taurite o ngā moroiti hei whakautu ki te wero DSS, i tohuhia e te hekenga o te rōpū Eubacterium_xylanophilum, Ruminococcaceae_UCG-014, Intestinimonas me Oscillibacter, me te pikinga o te Akkermansia me Prevotellaceae_UCG-001.
Ahua 4 Ka whakarerekē te BLG i te nui o ngā moroiti puku i roto i ngā kiore colitis i puta mai i te DSS.(A) Te nui o ngā moroiti puku i te taumata phylum; (B) Te nui o ngā moroiti puku i te taumata whānau; (C) Te nui o ngā moroiti puku i te taumata puninga. Ka whakaatuhia ngā raraunga hei toharite ± SEM (n = 6).#p < 0.05 ###p < 0.001 rānei vs rōpū mana (Con); *p < 0.05 **p < 0.01 rānei ***p < 0.001 rānei vs rōpū DSS.
I te mea ko ngā waikawa ngako mekameka-poto (SCFA) ngā matū whakaputa nui o Akkermansia me Prevotellaceae_UCG-001, ko te acetate, te propionate me te butyrate ngā SCFA tino nui i roto i te lumen whekau, 25-27 kei roto tonu mātou i tā mātou rangahau. E ai ki te Whakaahua 5, i tino heke te kukū o te acetate paru, te propionate, me te butyrate i roto i te rōpū i rongoatia ki te DSS, i te mea ka taea e te maimoatanga BLG te pehi i tēnei whakahekenga.
Pikitia 5. Ka whakanuia e te BLG ngā taumata o ngā SCFA i roto i ngā paru o ngā kiore me te mate puku i puta mai i te DSS.(A) Te nui o te waikawa acetic i roto i ngā paru; (B) te nui o te waikawa propionic i roto i ngā paru; (C) te nui o te waikawa butyric i roto i ngā paru. Ka whakaatuhia ngā raraunga hei toharite ± SEM (n = 6).#p < 0.05 ##p < 0.01 rānei vs rōpū mana (Con); *p < 0.05 **p < 0.01 rānei vs rōpū DSS.
I tatauhia anō e mātou te tauwehenga hononga Pearson i waenga i te SCFA rerekētanga taumata-ira me te microbiota paru. E ai ki te whakaaturanga i te Pikitia 6, he hononga pai a Akkermansia ki te whakaputanga o te waikawa propionic (Pearson = 0.4866) me te waikawa butyric (Pearson = 0.6192). He rerekē, he hononga kino a Enteromonas me Oscillobacter ki te whakaputanga acetate, me ngā tauwehenga Pearson o 0.4709 me 0.5104, ia. Waihoki, he hononga kino a Ruminococcaceae_UCG-014 ki te whakaputanga o te waikawa propionic (Pearson = 0.4508) me te waikawa butyric (Pearson = 0.5842), ia.
Ahua 6 Tātaritanga hononga Pearson i waenga i ngā SCFA rerekē me ngā moroiti koroni. (A) Enteromonas me te waikawa acetic; (B) Bacillus concussion me te waikawa acetic; (C) Akkermansia vs waikawa propionic; (D) Ruminococcus_UCG-014 me te waikawa propionic; (E) Akkermansia me te waikawa butyric; (F) ) Ruminococcus _UCG-014 me te waikawa butyric.
Ko te Glucagon-like peptide-1 (GLP-1) he hua whakaputa-muri motuhake-momo pūtau o te proglucagon (Gcg) me ngā āhuatanga ārai-mumura.28 E ai ki te whakaaturanga i te Pikitia 7, i puta he hekenga nui i roto i te whakaaturanga mRNA Gcg i te DSS. Ka taea e te maimoatanga koroni me te BLG te whakakore i te whakahekenga Gcg i puta mai i te DSS ki te whakataurite ki te rōpū whakahaere (Pikitia 7A). I ​​taua wā anō, i tino heke te taumata o te GLP-1 i roto i te toto i roto i te rōpū i rongoatia ki te DSS, ā, ka taea e te maimoatanga BLG te aukati i tēnei whakahekenga (Pikitia 7B). Mai i te mea ka taea e ngā waikawa ngako mekameka-poto te whakaoho i te hunanga GLP-1 mā te whakahohenga G-protein-coupled receptor 43 (GRP43) me te G-protein-coupled receptor 41 (GRP41), i tirotirohia hoki e mātou a GPR41 me GRP43 i roto i te koroni o ngā kiore colitis, ā, i kitea kua tino heke te whakaaturanga mRNA koroni o GRP43 me GPR41 i muri i te wero DSS, ā, ka taea e te maimoatanga BLG te whakaora i ēnei hekenga (Pikitia 7C). me D).
Ahua 7 Ka whakanui ake te BLG i ngā taumata GLP-1 toto me te whakaaturanga mRNA Gcg koroni, GPR41 me te GRP43 i roto i ngā kiore i rongoatia ki te DSS.(A) Whakaaturanga mRNA Gcg i roto i te kiko koroni; (B) Taumata GLP-1 i roto i te toto; (C) Whakaaturanga mRNA GPR41 i roto i te kiko koroni; (D) Whakaaturanga mRNA GPR43 i roto i te kiko koroni. Ka whakaatuhia ngā raraunga hei toharite ± SEM (n = 5–6).#p < 0.05, ##p < 0.01 rānei vs rōpū mana (Con); *p < 0.05 vs rōpū DSS.
I te mea ka taea e te maimoatanga BLG te whakanui ake i ngā taumata GLP-1 i roto i te toto, te whakaaturanga mRNA Gcg koroni, me ngā taumata SCFA paru i roto i ngā kiore i rongoatia ki te DSS, i tirotirohia e mātou te acetate, te propionate, me te butyrate tae atu ki ngā kiore mana (F-Con), DSS colitis (F-Con) -DSS) me te colitis i rongoatia ki te BLG (F-BLG) i runga i te tukunga o te GLP-1 mai i ngā pūtau epithelial koroni kiore tuatahi. E ai ki te whakaaturanga i te Pikitia 8A, ko ngā pūtau epithelial koroni kiore tuatahi i rongoatia ki te 2 mM waikawa acetic, te waikawa propionic, me te waikawa butyric, ia, i tino whakaoho i te tukunga o te GLP-1, e rite ana ki ngā rangahau o mua.29,30 Waihoki, ko ngā F-Con, F-DSS, me F-BLG katoa (he rite ki te 0.25 g o ngā paru) i tino whakaoho i te tukunga o te GLP-1 mai i ngā pūtau epithelial koroni kiore tuatahi. He mea nui, ko te nui o te GLP-1 i tukuna e ngā pūtau epithelial koroni kiore tuatahi i rongoatia ki te F-DSS he iti iho i te F-Con me te F-BLG tuatahi i rongoatia ki te F-BLG. ngā pūtau epithelial koroni kiore. (Pikitia 8B). E whakaatu ana ēnei raraunga i whakahokia mai e te maimoatanga BLG te hanga GLP-1 i ahu mai i te SCFA i roto i te puku.
Pikitia 8 Ko te SCFA i ahu mai i te BLG ka whakaoho i te tukunga o te GLP-1 mai i ngā pūtau epithelial koroni kiore tuatahi.(A) I whakaoho te waikawa acetic, te waikawa propionic, me te waikawa butyric i te tukunga o te GLP-1 mai i ngā pūtau epithelial koroni kiore tuatahi; (B) ngā tango paru i whakaohohia e te F-Con, F-DSS me te F-BLG ngā pūtau epithelial koroni kiore tuatahi Te nui o te GLP-1 i tukuna. I whakanohoia ngā wāhanga o ngā pūtau epithelial koroni ki roto i ngā rihi petri raro-karaihe, ā, i rongoatia ki te 2 mM waikawa acetic, te waikawa propionic, te waikawa butyric, me ngā tango paru F-Con, F-DSS, me te F-BLG (he rite ki te 0.25 g paru), ia. 2 hāora i te 37°C, 5% CO2, ia. Ko te nui o te GLP-1 i tukuna mai i ngā pūtau epithelial koroni kiore tuatahi i kitea e te ELISA. Ka whakaatuhia ngā raraunga hei toharite ± SEM (n = 3).#p < 0.05 ##p < 0.01 rānei vs. pātea, F-Con rānei; *p < 0.05 ki te F-DSS.
Ngā Whakarāpopototanga: Ace, waikawa acetic; Pro, waikawa propionic; heoi anō, waikawa butyric; F-Con, tangohanga paru mai i ngā kiore whakahaere; F-DSS, tangohanga paru mai i ngā kiore colitis; F-BLG, mai i te koroni i rongoatia ki te BLG Ngā tangohanga paru o ngā kiore mumura.
Kua whakarārangihia e te World Health Organization hei mate uaua ki te hopu, ā, kei te noho hei tūponotanga ā-ao te UC; Heoi anō, he iti tonu ngā tikanga whai hua mō te matapae, te ārai, me te rongoā i te mate. Nō reira, he hiahia nui kia tūhuratia, kia whakawhanakehia hoki ngā rautaki rongoā hou haumaru, whai hua hoki mō te UC. He kōwhiringa whai hua ngā whakaritenga rongoā Hainamana tuku iho nā te mea he maha ngā whakaritenga rongoā Hainamana tuku iho kua whakaatuhia he whai hua ki te rongoā i te UC i roto i te taupori Hainamana i roto i ngā rautau, ā, he mea koiora katoa me ngā rauemi taiao kāore e kino ki te tangata me ngā kararehe.31,32 Ko te whāinga o tēnei rangahau he rapu i tētahi whakaritenga rongoā Hainamana tuku iho haumaru, whai hua hoki mō te rongoā i te UC me te tūhura i tana tikanga mahi. Ko te BLG he tikanga otaota Hainamana rongonui e whakamahia ana hei rongoā i te rewharewha.8,33 Kua whakaatuhia e te mahi i roto i tā mātou taiwhanga me ētahi atu ko te indigo, he hua rongoā Hainamana tuku iho tukatukahia mai i te rauemi mata kotahi me te BLG, he whai hua nui ki te rongoā i te UC i roto i te tangata me ngā kararehe.4,34 Heoi anō, kāore i te mārama te tikanga o ngā pānga anti-colitis o te BLG me ōna pānga.I roto i te rangahau o nāianei, e whakaatu ana ā mātou hua ka whakaitihia e te BLG te mumura koroni i puta mai i te DSS, e pā ana ki te whakarerekētanga o te microbiota puku me te whakaora o te hanga GLP-1 mai i te puku.
E mōhiotia whānuitia ana ko te UC e tohuhia ana e ngā wā hokihoki me ngā āhuatanga haumanu noa, pērā i te whakahekenga taumaha, te mate korere, te toto i te rectum, me te kino nui o te mucosal colon.35 Nō reira, i whakahaerehia te colitis hokihoki mau tonu mā te whakahaere i ngā huringa e toru o te 1.8% DSS mō ngā rā e rima, ā, i muri mai ko te whitu rā o te inu wai. E ai ki te Whakaahua 1B, ko te whakahekenga taumaha me ngā kaute DAI e tohu ana i te angitu o te whakaoho i te colitis hokihoki mau tonu. Ko ngā kiore i roto i te rōpū i rongoatia ki te BLG i whakaatu i te whakaoranga piki mai i te rā 8, he rerekē rawa atu i te rā 24. I kitea anō hoki ngā huringa ōrite i roto i te kaute DAI, e kī ana he whakapainga ake i roto i te whakapainga haumanu o te colitis. Mō te whara o te koroni me te tūnga mumura, ko te roa o te koroni, te kino o te kiko koroni, me te whakaaturanga ira me te whakaputanga o ngā cytokines proinflammatory TNF-α, IL-1β, me te IL-6 i roto i te kiko koroni i tino pai ake i muri i te maimoatanga BLG. I te katoa, e whakaatu mārama ana ēnei hua he whai hua te BLG ki te maimoatanga o te colitis hokihoki mau tonu i roto i ngā kiore.
Me pēhea te whakamahi a te BLG i ōna pānga rongoā? He maha ngā rangahau o mua kua whakaatu he mahi nui tā te microbiota puku i roto i te pathogenesis o te UC, ā, kua puta ake ngā maimoatanga e hangai ana ki te microbiome me te microbiome-arotahi hei rautaki tino ataahua mō te maimoatanga o te UC. I roto i tēnei rangahau, i whakaaturia e mātou ko te maimoatanga BLG i hua ake ai he huringa nui i roto i te hanganga o te microbiota puku, e kī ana ko te pānga tiaki o te BLG ki te colitis i puta mai i te DSS e pā ana ki te whakarerekētanga o te microbiota puku. He rite tēnei kitenga ki te whakaaro ko te whakahou i te homeostasis o te microbiota puku he huarahi nui ki te mārama ki te whai huatanga o ngā whakaritenga TCM.36,37 He mea nui, ko te Akkermansia he huakita Gram-negative me te tino anaerobic e noho ana i roto i te paparanga mucus o te puku, e whakaiti ana i ngā mucins, e whakaputa ana i te waikawa propionic, e whakaoho ana i te rerekētanga o ngā pūtau goblet, ā, e pupuri ana i te mahi o te ārai mucosa.26 He maha ngā raraunga haumanu me ngā raraunga kararehe e kī ana he hononga nui a Akkermansia ki te mucosa hauora,38 me te whakahaere ā-waha o Akkermansia spp. ka taea te whakapai ake i te mumura o te mucosal.39 E kī ana ā mātou raraunga o nāianei kua tino piki ake te nui o te Akkermansia i muri i te maimoatanga BLG. Hei tāpiri, ko Prevotellaceae_UCG-001 he huakita whakaputa SCFA.27 He maha ngā rangahau i whakaatu i kitea a Prevotellaceae_UCG-001 i roto i te nui iti i roto i ngā paru o ngā kararehe me te colitis.40,41 E whakaatu ana hoki ā mātou raraunga o nāianei ka taea e te maimoatanga BLG te whakanui ake i te nui o te Prevotellaceae_UCG-001 i roto i te koroni o ngā kiore i rongoatia ki te DSS. He rerekē, ko Oscillibacter he huakita mesophilic, he tino anaerobic.42 i kōrerohia ko te nui o te Oscillibacter i tino piki ake i roto i ngā kiore UC, ā, he hononga pai ki ngā taumata IL-6 me te IL-1β me ngā kaute pathological.43,44 He mea nui, i whakaitihia e te maimoatanga BLG te nui o te Oscillibacter i roto i ngā paru o ngā kiore i rongoatia ki te DSS. He mea nui, ko ēnei huakita i whakarerekētia e te BLG ngā huakita tino whakaputa SCFA. He maha ngā o mua Kua whakaatuhia e ngā rangahau ngā pānga pai pea o ngā SCFA ki te mumura o te koroni me te tiaki i te kounga o te epithelial o te puku.45,46 I kitea anō hoki e ā mātou raraunga o nāianei ko ngā kukū o te SCFA acetate, propionate, me te butyrate i roto i ngā paru i rongoatia ki te DSS i tino piki ake i roto i ngā kiore i rongoatia ki te BLG. Ina huihuia, e whakaatu mārama ana ēnei kitenga ka taea e te maimoatanga BLG te whakarei ake i ngā huakita SCFA i puta mai i te DSS i roto i ngā kiore me te colitis e hoki whakamuri ana.
Ko te GLP-1 he incretin e hangaia ana i roto i te ileum me te koroni, ā, he mahi nui tāna ki te whakaroa i te whakawātea o te puku me te whakaheke i te huka toto i muri i te kai.47 E whakaatu ana ngā taunakitanga ka taea e te dipeptidyl peptidase (DPP)-4, he agonist receptor GLP-1, me te nanomedicine GLP-1 te whakamamae i te mumura o te puku i roto i ngā kiore.48-51 E ai ki ngā rangahau o mua, i honoa ngā kukū SCFA teitei ki ngā taumata GLP-1 plasma i roto i te tangata me ngā kiore. 52 E whakaatu ana ā mātou raraunga o nāianei i muri i te maimoatanga BLG, i tino piki ake ngā taumata GLP-1 serum me te whakaaturanga mRNA Gcg. Waihoki, i tino piki ake te hunanga GLP-1 i roto i ngā ahurea koroni i muri i te whakaohooho me ngā tango paru mai i ngā kiore colitis i rongoatia ki te BLG ki te whakataurite ki te whakaohooho me ngā tango paru mai i ngā kiore colitis i rongoatia ki te DSS. He aha te pānga o ngā SCFA ki te tukunga o te GLP-1? Gwen Tolhurst et al. I kōrerotia ka taea e te SCFA te whakaoho i te whakaputanga GLP-1 mā te GRP43 me te GPR41.29 E whakaatu ana hoki ā mātou raraunga o nāianei ka whakanuia e te maimoatanga BLG te whakaaturanga mRNA o te GRP43 me te GPR41 i roto i te koroni o ngā kiore i rongoatia ki te DSS. E kī ana ēnei raraunga ka taea e te maimoatanga BLG te whakaora i te hanga GLP-1 i whakatairangatia e te SCFA mā te whakahohe i te GRP43 me te GPR41.
He rongoā roa te BLG, he rongoā kore-tohu (OTC) i Haina. Ko te horopeta mōrahi o te BLG e whakaaetia ana i roto i ngā kiore Kunming he 80g/Kg, ā, kāore anō kia kitea he paitini nui.53 I tēnei wā, ko te horopeta e taunakitia ana mō te BLG (kāore he huka) i roto i te tangata he 9-15 g/rā (3 ngā wā i te rā). I whakaatuhia e tā mātou rangahau i whakapai ake te BLG i te 1g/Kg i te mate puku roa i puta mai i te DSS i roto i ngā kiore. He tata tēnei horopeta ki te horopeta BLG e whakamahia ana i roto i te haumanu. I kitea anō e tā mātou rangahau ko tana tikanga mahi he mea whakawhitiwhiti, i te iti rawa i tetahi wāhanga, e ngā whakarerekētanga i roto i te microbiota puku, inā koa ko ngā huakita whakaputa SCFA, pērā i a Akkermansia me Prevotellaceae_UCG-001, hei whakaora i te hanga GLP-1 i ahu mai i te puku. E kī ana ēnei kitenga me whai whakaaro anō ki te BLG hei rongoā pea mō te maimoatanga o te mate puku haumanu. Heoi, ko te tikanga tika e whakarerekē ai i te microbiota puku me whakaū tonu mā ngā kiore kāore i te nui te microbiota me te whakawhitinga huakita paru.
Ace, waikawa acetic; but, waikawa butyric; BLG, pandan; DSS, dextran sodium sulfate; DAI, taupū mahi mate; DPP, dipeptidyl peptidase; FID, pūoko ionization mura; F-Con, whakahaere Ngā tango paru o ngā kiore; F-DSS, ngā tango paru o ngā kiore colitis DSS; F-BLG, ngā tango paru o ngā kiore colitis i rongoatia ki te BLG; GLP-1, glucagon-rite peptide-1; Gcg, glucagon; chromatography hau, chromatography hau; GRP43, G protein-coupled receptor 43; GRP41, G protein-coupled receptor 41; H&E, hematoxylin-eosin; HBSS, Hanks' Balanced Salt Solution; OTC, OTC; PCA, tātaritanga wāhanga matua; PCoA, tātaritanga taunga matua; Pro, waikawa propionic; SASP, sulfasalazine; SCFA, waikawa ngako mekameka-poto; Rongoā Hainamana, rongoā tuku iho Hainamana; UC, ulcerative colitis.
I whakaaetia ngā tikanga whakamātautau katoa e te Komiti Matatika Kararehe o te Whare Wānanga o Peking Shenzhen-Hong Kong University of Science and Technology Medical Center (Shenzhen, Haina) e ai ki ngā Aratohu Whare me ngā Ture Kararehe (nama matatika A2020157).
He nui ngā takoha a ngā kaituhi katoa ki te ariā me te hoahoa, te kohikohi raraunga, te tātari raraunga me te whakamārama; i whai wāhi ki te tuhi i te tuhinga, ki te arotake arohaehae rānei i ngā ihirangi hinengaro nui; i whakaae ki te tuku i te tuhinga ki te hautaka o nāianei; i te mutunga i whakaaetia te putanga mō te whakaputanga; i te kawenga mō ngā āhuatanga katoa o te mahi.
I tautokona tēnei mahi e te National Natural Science Foundation of China (81560676 me 81660479), te kaupapa tino pai o Te Whare Wānanga o Shenzhen (86000000210), te Shenzhen Science and Technology Auahatanga Committee Fund (JCYJ20210324093810026), me te Guangdong Provincial Medical Science and Technology Research Fund (A2020157 me A2020272), Guizhou Medical University Pharmacy Guizhou Province I tautokona e Key Laboratory (YWZJ2020-01) me Peking University Shenzhen Hospital (JCYJ2018009).
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