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Ban-Lan-Gen nibii bibii lɛ haa dextran sodium sulfate-ni kɛ tsɛŋemɔ hela ni baa mɔ mli lɛ baa shi yɛ tsɛŋemɔ hela mli kɛtsɔ tsɛŋemɔ hela ni yɔɔ tsɛŋemɔ hela mli lɛ tsakemɔ kɛ tsɛŋemɔ hela ni jɛɔ tsɛŋemɔ hela ni jɛɔ GLP-1 mli lɛ mli baa lɛ nɔ
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 Haitao21Peking University Shenzhen Hospital Department of Pharmacy, Shenzhen; 2Shenzhen Yunivɛsiti Hewalɛ He Nilee He Skul ni Kwɛɔ Tsofafeemɔ Nɔ, Shenzhen, China Maŋ lɛ; 3Guizhou Tsofafeemɔ He Nikasemɔhe lɛ Engineering Technology Nibii Amli Taomɔ He ni kɔɔ Akutseiaŋ Tsofafeemɔ kɛ Kusum Chinese Tsofafeemɔ He Nitsumɔ kɛ Nitsumɔ He Nikasemɔ He Nitsumɔhe lɛ, Guizhou Kpokpaa lɛ nɔ Tsofafeemɔ He Nitsumɔhe Titri lɛ, Guizhou Tsofafeemɔ He Nikasemɔhe lɛ , Guiyang, People’s Republic of China; 4 Nitsumɔhe ni Kwɛɔ Musu Mli Nibii Anɔ lɛ, Peking Yunivɛsiti Shenzhen Helatsamɔhe lɛ, Shenzhen, China maŋ lɛ; 5 Tsofafeemɔ Skul, Guizhou Tsofafeemɔ Yunivɛsiti, Maŋ lɛ Tsofafeemɔ Tsofafeemɔ He Nitsumɔ kɛ Nitsumɔ He Nitsumɔhe Titri, Guiyang; 6 Nitsumɔhe ni Kwɛɔ Tsofafeemɔ He Nitsumɔhe lɛ, Peking Yunivɛsiti Shenzhen Helatsamɔhe lɛ, Shenzhen, China [email buɔ he] Shen Xiangchun, Tsofafeemɔ Skul, Guizhou Tsofafeemɔ Yunivɛsiti, Guizhou, People’s Republic of China, 550004, Email [email buɔ he] Otii: GLP-1-ni ji tsofafeemɔ gbɛ hee ko ni akɛtsuɔ nii kɛtsaa helai ni haa mɔ he jɔ̃ɔ ehe lɛ hela.Ban-Lan-Gen (BLG) granules ji tsofa ko ni ale ni gbeɔ helai ni ji TCM ni jieɔ bɔ ni ebaanyɛ ekɛ helai ni haa mɔ he jɔ̃ɔ ehe lɛ atsu nii yɛ helai srɔtoi ni haa mɔ he jɔ̃ɔ ehe lɛ atsamɔ mli lɛ kpo.Shi kɛlɛ, bɔ ni etsuɔ ​​nii ehaa yɛ helai ni haa mɔ he jɔ̃ɔ ehe lɛ anɔ kɛ bɔ ni etsuɔ ​​nii eha lɛ bɛ faŋŋ lolo.M (DSS)-ni ha hela ni haa mɔ he jɔ̃ɔ ehe ni sɛɛ tsɛɔ lɛ baa yɛ ŋmeii amli. gut microbiota mli nibii, fecal SCFAs ŋwɛibɔfoi, kɛ GLP-1 ni ajieɔ kɛjɛɔ shishijee ŋwɛibɔfoi amli wala yibii amli SCFA-ni jɛɔ GLP-1 mli baa lɛ mli. Kɛfata he lɛ, BLG helatsamɔ baanyɛ aha Gcg, GPR41 kɛ GRP43 kpojiemɔ kɛ lá mli GLP-1 lɛ aya hiɛ jogbaŋŋ yɛ fɔmɔ kotoku mli, kɛtsɔ SCFA-ni feɔ helatsɛmɛi tamɔ Akkermansia kɛ Prevotellaceae_UCG-001 lɛ nɔyaa nɔ, kɛ helatsɛmɛi babaoo ni baa shi lɛ nɔ. Eubacteria_xylanophilum_kuu, Ruminokokaseae_UCG-014, Musu mli hela kɛ Oscillibacter. Kɛfata he lɛ, BLG helatsamɔ baanyɛ aha SCFAs ni yɔɔ colitis ŋmeii amli lɛ aya hiɛ waa. Yɛ nakai beaŋ nɔŋŋ lɛ, shikpamɔi ni afee yɛ vitro mli lɛ hu tsɔɔ akɛ, BLG ni akɛtsaa ŋmeii lɛ amli nu lɛ baanyɛ akanya Murine colonic epithelial cells bibii lɛ ni amɛjie GLP-1 lɛ waa. Mumɔ mli wiemɔi: Nibii ni ana nɛɛ tsɔɔ akɛ BLG yɛ hewalɛ ni gbeɔ hela ni haa mɔ mli fũuɔ lɛ. BLG yɛ nyɛmɔ ni akɛbaatsu nii akɛ tsofafeemɔ gbɛ, kɛ hoo lɛ, yɛ fã ko mli kɛtsɔ gut microbiota lɛ tsakemɔ kɛ gut mli SCFA-ni jɛ GLP-1 feemɔ mli lɛ nɔ Tsofai ni woɔ shi kɛha colitis ni sɛɛ tsɛɔ ni baa ekoŋŋ lɛ nɔ. Wiemɔi titrii: fɔmɔ kotoku mli hela, Ban-Lan-Gen bibii, fɔmɔ kotoku mli nibii bibii, fɔmɔ nii ni yɔɔ kuku, GLP-1.
Ulcerative colitis (UC) ji hela ko ni haa mɔ mli fũuɔ be kakadaŋŋ ni haa mɔ mli fũuɔ shii abɔ, musu mli piŋmɔ, shwiili mli shwiili, kɛ shwiili mli lá ni hoɔ. Nɛkɛ yifalɛ nɛɛ kɛ naagbai wuji baa maŋ hewalɛnamɔ nɔ ni eyɛ naagbai ni mli wa waa kɛha helatsɛmɛi lɛ anyɛmifeemɔ ni amɛkɛtsu nii kɛ amɛshihilɛ mli shihilɛ. kɛha UC, ni oti ni ma tsofafeemɔ hiɛ ji yɛ helatsamɔhe lɛ ni akudɔ helatsamɔhe okadii lɛ, ni ekɛ eshaifaa aba ni ekwɛ nɔ, ni ewo mucosal tsamɔ he hewalɛ, ni ekɛba shi ekoŋŋ. Nyɛsɛɛ nɛɛ, saji babaoo ni akase lɛ etsɔɔ akɛ, Chinese tsofafeemɔ (TCM) lɛ ejie nyɛmɔ babaoo kpo yɛ yelikɛbuamɔ ni ekɛjieɔ UC ni tsofai fɔji ni yɔɔ mli lɛ faaa lɛ mli, ni etsɔɔ akɛ TCM tsofafeemɔ gbɛi heei ni afee lɛ ji tsofafeemɔ gbɛ ni hi jogbaŋŋ kɛha UC.5-7 .
Banlangen Granules (BLG) ji Chinese tsofa ko ni akɛ nu ni ajieɔ kɛjɛɔ Banlangen shishifã lɛ mli lɛ feɔ.8 Kɛfata he lɛ, BLG jieɔ bɔ ni etsuɔ ​​nii jogbaŋŋ ehaa yɛ helai srɔtoi ni haa mɔ mli fũuɔ lɛ ahe lɛ kpo.9,10 Kɛfata he lɛ, procobinit,S-R- 11,12 Nikasemɔi ni eho lɛ etsɔɔ jogbaŋŋ akɛ, nibii ni yɔɔ Radix isatidis mli lɛ amli nu lɛ mli nibii ni ajieɔ kɛjɛɔ nu mli lɛ, kɛ nucleosides (hypoxanthine, adenosine, uridine kɛ guanosine) kɛ indigo alkaloids tamɔ indigo kɛ indirubin. 13-17 Shi kɛlɛ, afeee nikasemɔ ko ni damɔ odaseyeli nɔ koni akɛpɛi bɔ ni BLG tsuɔ nii jogbaŋŋ ehaa yɛ tsɛŋemɔ hela mli lɛ mli. tsɛŋemɔ hela ni haa mɔ mli fũuɔ, ni egbɛjianɔtoo lɛ kɛ gut microbiota lɛ tsakemɔ kɛ gut mli glucagon-like peptide-1 (GLP-1) ni afeɔ lɛ ekoŋŋ lɛ yɔɔ tsakpaa.
Akɛ BLG ŋmeii (ni sugar bɛ mli, ni NMPA kpɛlɛ Z11020357 nɔ; Louis, MO, USA). kɛ tsɔne ni haa mɔ he jɔɔ lɛ lɛ, ahé kɛjɛ Aladdin nitsumɔhei (Shanghai, China).2-Ahe tsɔne ni akɛwoɔ tsɔne mli lɛ kɛjɛ Merck KGaA (Darmstadt, Germany).
18-22 g) ni akɛwo Beijing Wetahe Laboratory Animal Technology Co., Ltd. nu kɛha otsi kome koni ekɛ ehe awo shihilɛ hee lɛ mli. No sɛɛ lɛ, aja ŋmeii lɛ amli awo kui ejwɛ mli: kuu ni kudɔɔ, DSS nɔkwɛmɔnɔ kuu, kuu ni akɛ SASP tsuɔ nii (200 mg/kg, oral) kɛ kuu ni akɛ BLG tsuɔ nii (1 g/kg, oral). 1.8% DSS ni ji 1.8% DSS lɛ sɛɛkuu etɛ kɛha gbii 5, ni nu ni ajie kɛjɛ mli lɛ nyiɛɔ sɛɛ gbii 7, taakɛ wɔ nikasemɔ ni eho lɛ tsɔɔ lɛ. g/kg.Yɛ nakai beaŋ lɛ, ato SASP lɛ falɛ lɛ he gbɛjianɔ yɛ 200 mg/Kg taakɛ woji lɛ tsɔɔ lɛ.4 Kuu ni kudɔɔ kɛ DSS nɔkwɛmɔnɔ kuu lɛ ná nu falɛ kome too lɛ nɔŋŋ yɛ kaa lɛ mli fɛɛ.
BLG haa DSS-ni haa mɔ he jɔ̃ɔ ehe lɛ yaa hiɛ yɛ tsinabii amli. (A) Shikpamɔ ni kɔɔ hela ni haa mɔ he jɔ̃ɔ ehe lɛ he kɛ tsamɔ, (B) gbɔmɔtso lɛ mli tsiimɔ tsakemɔ, (C) hela nitsumɔ he okadi (DAI) yibɔ, (D) mɔ mli lɛlɛ, (E) mɔ mli mfoniri ni damɔ shi kɛha Col&E × Colion (H0) (G) histological skor.Akɛ saji lɛ haa akɛ nɔ ni tsɔɔ ± SEM (n = 6). *p < 0.05 loo **p < 0.01 loo ***p < 0.001 kɛ DSS kuu lɛ.
Akɛ gbɔmɔtso lɛ mli tsiimɔ, shwiili mli lá ni hoɔ, kɛ lá ni hoɔ yɛ fɔmɔ kotoku lɛ mli lɛ wo wolo nɔ daa gbi.
Akɛ formalin wo fɔmɔ kotoku lɛ mli ni akɛwo paraffin mli.
Akɛ Trizol reagent (Invitrogen, Carlsbad, CA) jieɔ RNA fɛɛ ni yɔɔ fɔmɔ kotoku lɛ mli lɛ, ni cDNA ni ajieɔ kɛjɛɔ mli lɛ nyiɛɔ sɛɛ (TaKaRa, Kusatsu, Shiga, Japan). akwɛ mli kɛtsɔ 2-ΔΔCT gbɛ nɔ. Atsɔɔ bɔ ni wala yibii lɛ yɔɔ ha lɛ mli yɛ Table 1 lɛ mli.
Yɛ kukufoo mli lɛ, ajie tsɛŋemɔ helai ni eye otsii 6-8 lɛ amli tsɛŋemɔ helai lɛ klɛŋklɛŋ yɛ afɔleshaa sɛɛ kɛtsɔ fɔmɔ kotoku lɛ mli ni ajieɔ lɛ nɔ, no sɛɛ lɛ agbeleɔ naa yɛ be kakadaŋŋ mli, ni akɛ Hanks Balanced Salt Solution (HBcium) kɛ mag- cut000, ni bɛ mli lɛ tsuɔ he nii. mm ni ji fãi bibii. 100 μg/mL streptomycin) yɛ 37 °C mli ni etsɔɔ nylon ŋtayaa ko mli (pore size ~250 μm). 5% CO2.
Akɛ PBS fee fãji ni yɔɔ fɔmɔ kotoku lɛ mli lɛ ekome, ni ana cytokines IL-6, TNF-α kɛ IL-1β ni yɔɔ fɔmɔ kotoku lɛ mli lɛ kɛtsɔ luminex ELISA assay kits (R&D gbɛjianɔtoi, Minneapolis, MN, USA) nɔ. (Bioswamp, Wuhan, China) taakɛ mɔ ni fee lɛ tsɔɔ lɛ.
Akɛ DNA fɛɛ ni ajieɔ kɛjɛɔ fɔmɔ kotoku mli lɛ tsu nii kɛtsɔ DNA ni ajieɔ kɛjɛɔ fɔmɔ kotoku mli lɛ nɔ (Tiangen, China). 806R (GGACTACHVGGGTWTCTAAT) ji nɔ ni akɛtsu nii koni akɛha V3-V4 kpokpai ni yɔɔ 16S rRNA lɛ mli lɛ aya hiɛ yɛ hei srɔtoi. 21,22 Yɛ kukufoo mli lɛ, akɛ Cutadapt (V1.9.1) tsu nii ni akɛjie faili ni atsɔɔ mli lɛ. chimeric sequences.Akɛ RDP mligbalamɔ tsɔne (http://rdp.cme.msu.edu/) ni damɔ SILVA ribosomal RNA tsɛŋemɔ hela he saji lɛ nɔ lɛ tsu nii kɛpɛi akutso lɛ mli nibii amlipɛimɔ kɛ mligbalamɔ mli.
Asusu tsɔne ni haa mɔ he jɔɔ lɛ (acetic acid, propionic acid, kɛ butyric acid) lɛ falɛ he tamɔ bɔ ni Tao kɛ ekrokomɛi tsɔɔ mli tsutsu lɛ, kɛ tsakemɔi komɛi. 2-ethylbutyric acid (mligbɛ shishitoo mla), no sɛɛ lɛ, afee lɛ ekome ni awo mli la yɛ 4°C. 12,000 rpm kɛha minitii 15 yɛ C. Akɛ ether 0.5 mL jieɔ nu ni hoɔ lɛ mli ni awoɔ GC lɛ mli koni akwɛ mli. (FID). mL/min.Injection volume ji 1 μL.Injector kɛ detector lɛ mli latsaa ji 300°C.Akɛ oven lɛ mli latsaa lɛ to 140°C nɔ minitii 13.5, no sɛɛ lɛ, etee hiɛ kɛyashɛ 250°C yɛ 120°C/min mli; aŋmɛ hulutsoo be lɛ mli minitii 5.
Akɛ saji lɛ haa akɛ shishitsɔɔmɔ ± tɔmɔ ni yɔɔ shishitoo mla lɛ mli (SEM).
No hewɔ lɛ, ato DSS-ni haa mɔ he jɔ̃ɔ ehe ni haa mɔ he jɔ̃ɔ ehe lɛ shishi koni akɛkwɛ bɔ ni BLG lɛ tsuɔ nii jogbaŋŋ ehaa yɛ DSSCo (Fig. 1A the group the group with DSSCo control) lɛ mli. 1B kɛ C).Colon shortening ji UC he okadi ko ni he hiaa waa. Histopathological mlipɛimɔ ji nɔ ni afee koni akɛkwɛ bɔ ni tsɛŋemɔ hela lɛ mli fũuɔ ehaa lɛ mli. g/Kg lɛ ji nɔ ni akɛtoɔ SASP lɛ he yɛ 200 mg/Kg.Kɛ abua naa lɛ, nibii ni ana nɛɛ tsɔɔ akɛ BLG tsuɔ nii jogbaŋŋ yɛ DSS-ni haa mɔ he jɔ̃ɔ ehe ni haa mɔ he jɔ̃ɔ ehe ni baa shi yɛ ŋmeii amli lɛ nɔbaa mli.
TNF-α, IL-1β kɛ IL-6 ji fũu he okadii ni he hiaa ni haa mɔ mli fũuɔ. Taakɛ atsɔɔ yɛ mfoniri 2A lɛ mli lɛ, DSS ha TNF-α, IL-1β kɛ IL-6 ni yɔɔ fɔmɔ kotoku lɛ mli lɛ tee hiɛ waa kɛ akɛto kuu ni kudɔɔ lɛ he. IL-1β, kɛ IL-6 ni yɔɔ fɔmɔ kotoku lɛ mli lɛ hu tsɔɔ akɛ TNF-α, IL-1β, kɛ IL-6 ni yɔɔ fɔmɔ kotoku lɛ mli lɛ tee hiɛ waa yɛ ŋmeii ni akɛ DSS tsuɔ nii ahaa amɛ lɛ amli, yɛ be mli ni BLG tsofafeemɔ lɛ ha nɛkɛ yifalɛ nɛɛ ba shi (Mfoniri 2B).
BLG tsiɔ tsɛŋemɔ helai ni haa mɔ he jɔ̃ɔ ehe ni ji TNF-α, IL-1β kɛ IL-6 lɛ afeemɔ naa yɛ tsɛŋemɔ helai ni akɛ DSS tsuɔ nii yɛ mli lɛ amli lɛ mli.(A) TNF-α, IL-1β kɛ IL-6 ni yɔɔ tsɛŋemɔ helai amli lɛ; (B) tsɛŋemɔ hela ni ji TNF-α, IL-1β kɛ IL-6 lɛ mli nibii ni yɔɔ tsɛŋemɔ hela mli lɛ. *p < 0.05 loo **p < 0.01 kɛ DSS kuu lɛ.
16S rRNA sequencing lɛ ji nɔ ni akɛpɛiɔ bacteria akutso ni yɔɔ gut mli nibii amli lɛ mli. (Mfoniri 3A).Agbɛnɛ hu, Chao1 index kɛ Shannon index ni atsɔɔ yɛ mfoniri 3B kɛ C lɛ mli lɛ tsɔɔ akɛ akutsoŋbii amli srɔtofeemɔ ni yɔɔ gut microbiota lɛ mli lɛ ba shi yɛ BLG-ni akɛtsaa ŋmeii lɛ amli, ejaakɛ Shannon index lɛ ba shi waa yɛ BLG-ni akɛtsaa kuu lɛ mli. patterns yɛ kui etɛ lɛ ateŋ ni etsɔɔ akɛ akutsoŋ gbɛjianɔtoo ni DSS-tsaa ŋmeii lɛ mli lɛ mli gbala faŋŋ yɛ BLG tsamɔ sɛɛ (Mfoniri 3D kɛ E).Nɛkɛ saji nɛɛ tsɔɔ akɛ BLG tsamɔ lɛ ná akutsoŋ gbɛjianɔtoo ni DSS-induced colitis yɔɔ mli lɛ nɔ hewalɛ waa.
BLG tsakeɔ gut microbiota srɔtoi ni yɔɔ ŋmeii ni DSS-ni kɛbaa lɛ amli lɛ amli.(A) Venn mfoniri ni kɔɔ OTU he, (B) Chao1 index, (C) Shannon ninamɔ he okadi, (D) OTU he nibii amlipɛimɔ (PCA) skor plot ni kɔɔ OTU he, (E) OTU Anasis skor PCo Coordinate. Akɛ saji lɛ haa akɛ nɔ ni tsɔɔ ± SEM (n = 6). ** p <0.01 kɛ DSS kuu lɛ.
Kɛha tsakemɔi pɔtɛɛ ni baa yɛ fɔmɔ kotoku mli lɛ mli lɛ, wɔpɛi bɔ ni fɔmɔ kotoku lɛ mli nibii bibii lɛ yɔɔ ha lɛ mli yɛ ŋwɛigbɛ nibii fɛɛ amli. Taakɛ atsɔɔ yɛ mfoniri 4A lɛ mli lɛ, phyla titri ni yɔɔ kui fɛɛ amli ji Firmicutes kɛ Bacteroidetes, ni Verrucomicrobia nyiɛɔ sɛɛ. akutsei ni DSS-tsaa ŋmeii lɛ kɛ ŋmeii ni kudɔɔ amɛ lɛ toɔ ŋmeii ni kudɔɔ amɛ lɛ ahe, ni nɛkɛ tsakemɔi nɛɛ tsake kwraa yɛ BLG helatsamɔ sɛɛ . 4B.Kɛ akɛto DSS kuu lɛ he lɛ, BLG ni baa shi lɛ ha Akkermansiaceae babaoo lɛ tee hiɛ, shi eha Lachnospiraceae kɛ Ruminococcaceae babaoo lɛ ba shi yɛ ŋwɛigbɛ. 4C. Nɛkɛ niiamlipɛimɔ nɛɛ hu tsɔɔ akɛ BLG helatsamɔ lɛ tsakeɔ nibii bibii ni wala yɔɔ amɛmli lɛ ni bɛ shiŋŋ lɛ jogbaŋŋ yɛ DSS kaa lɛ hetoohamɔ mli, ni Eubalynouplac lɛ baa shi. Ruminococcaceae_UCG-014, fɔmɔ kotoku mli helai kɛ Oscillibacter, kɛ Akkermansia kɛ Prevotellaceae_UCG-001 ni yaa hiɛ.
BLG tsakeɔ gut mli nibii bibii ni fa babaoo yɛ DSS-ni haa mɔ he jɔ̃ɔ ehe lɛ mli.(A) gut mli nibii bibii babaoo ni yɔɔ phylum lɛ mli; (B) Gut microbiota babaoo ni yɔɔ weku lɛ mli; (C) Nibii bibii ni yɔɔ fɔmɔ kotoku lɛ mli lɛ babaoo yɛ tsɛŋemɔ hela lɛ mli.Akɛ saji lɛ haa akɛ nɔ ni tsɔɔ ± SEM (n = 6). *p < 0.05 loo **p < 0.01 loo ***p < 0.001 kɛ DSS kuu lɛ.
25-27 Wɔyɛ wɔ nikasemɔ lɛ mli lolo. lɛ nɔ baa shi waa yɛ kuu ni akɛ DSS tsuɔ nii yɛ mli lɛ mli, yɛ be mli ni BLG tsamɔ baanyɛ atsĩ nɛkɛ nɔ ni baa shi nɛɛ naa babaoo.
BLG haa SCFAs lɛ falɛ yaa hiɛ yɛ ŋmeii ni DSS-induced colitis yɔɔ mli lɛ amli.(A) Acetic acid ni yɔɔ ŋmeii amli; (B) propionic acid ni yɔɔ fɔmɔ kotoku mli lɛ; (C) butyric acid ni yɔɔ fɔmɔ kotoku mli lɛ.Akɛ saji lɛ haa akɛ nɔ ni tsɔɔ ± SEM (n = 6). *p < 0.05 loo **p < 0.01 kɛ DSS kuu lɛ.
Wɔtee nɔ wɔbu Pearson tsakpaa ni yɔɔ srɔtofeemɔ ni yɔɔ SCFA kɛ fecal microbiota teŋ lɛ he akɔntaa. 0.4709 kɛ 0.5104, yɛ gbɛ kome nɔ.Nakai nɔŋŋ hu, Ruminococcaceae_UCG-014 kɛ propionic acid (Pearson = 0.4508) kɛ butyric acid (Pearson =4.0) nifeemɔ lɛ bɛ tsakpaa ko ni ehiii.
Pearson tsakpaa mlipɛimɔ ni ka SCFAs sɔrɔtoi kɛ tsɛŋemɔ helai bibii ni yɔɔ fɔmɔ kotoku mli lɛ ateŋ.(A) Enteromonas ni acetic acid yɔɔ mli; (B) Bacillus ni haa mɔ tsui nyɔɔ emli ni akɛ acetic acid woɔ mli; (C) Akkermansia kɛ propionic asid; (D) Ruminococcus_UCG-014 ni akɛ tsɔne ni haa mɔ he jɔɔ lɛ tsuɔ nii; (E) Akkermansia ni akɛ butyric acid ewo mli lɛ; (F) ) Ruminococcus _UCG-014 ni akɛ tsofa ni haa mɔ he jɔɔ lɛ tsuɔ nii.
Taakɛ atsɔɔ yɛ mfoniri 7 lɛ mli lɛ, DSS ha Gcg mRNA kpojiemɔ lɛ nɔ ba shi waa. (Mfoniri 7A).Yɛ nakai beaŋ nɔŋŋ lɛ, GLP-1 ni yɔɔ lá mli lɛ ba shi kwraa yɛ kuu ni akɛ DSS tsuɔ nii yɛ mli lɛ mli, ni BLG tsamɔ baanyɛ atsĩ nɛkɛ shibaa nɛɛ naa babaoo (Mfoniri 7B). 41 (GRP41) nitsumɔ, wɔ hu wɔpɛi GPR41 kɛ GRP43 mli yɛ colitis ŋmeii lɛ amli ni wɔna akɛ colonic mRNA ni ajieɔ lɛ kpo yɛ GRP43 kɛ GPR41 lɛ mli lɛ ba shi waa yɛ DSS kaa lɛ sɛɛ, ni BLG helatsamɔ baanyɛ ajie nɛkɛ shigbeemɔi nɛɛ jogbaŋŋ kɛ DC (Mfoniri 7).
BLG haa lá mli GLP-1 lɛ yaa hiɛ, ni Gcg, GPR41 kɛ GRP43 mRNA ni ajieɔ lɛ kpo yɛ tsɛŋemɔ hela ni akɛ DSS tsuɔ nii yɛ mli lɛ mli lɛ yaa hiɛ.(A) Gcg mRNA ni ajieɔ lɛ kpo yɛ tsɛŋemɔ hela mli; (B) GLP-1 ni yɔɔ lá mli lɛ mli; (C) GPR41 mRNA kpojiemɔ yɛ fɔmɔ kotoku mli; (D) GPR43 mRNA kpojiemɔ yɛ fɔmɔ kotoku mli.Akɛ saji lɛ haa akɛ nɔ ni tsɔɔ ± SEM (n = 5–6). *p < 0.05 kɛ DSS kuu lɛ.
Akɛni BLG helatsamɔ baanyɛ aha lá mli GLP-1 lɛ aya hiɛ, Gcg mRNA ni ajieɔ lɛ kpo, kɛ SCFA ni yɔɔ fɔmɔ kotoku lɛ mli lɛ aya hiɛ yɛ DSS-tsamɔ mli hewɔ lɛ, wɔtee nɔ wɔpɛi acetate, propionate, kɛ butyrate mli kɛ agbɛnɛ hu kɛjɛ nɔyeli (F-Con), DSS colitis (F-Con) -DSS) kɛ coBLGtisce ni ji BLG- GLP-1 kɛjɛ shishijee tsɛŋemɔ hela mli wala yibii lɛ amli.Taakɛ atsɔɔ yɛ mfoniri 8A lɛ mli lɛ, shishijee tsɛŋemɔ hela mli wala yibii ni akɛ 2 mM acetic acid, propionic acid, kɛ butyric acid tsuɔ he nii lɛ, haa GLP-1 lɛ jieɔ ehe kpo waa, ni ekɛ nikasemɔi ni eho lɛ kpãa gbee. (ni kɛ 0.25 g ni ji ŋmei yeɔ egbɔ) lɛ tsirɛɔ GLP-1 ni ajieɔ kɛjɛɔ shishijee murine mli wala yibii lɛ amli lɛ waa. Nɔ ni sa kadimɔ ji akɛ, GLP-1 ni F-DSS-ni akɛtsaa shishijee ŋmei mli wala yibii lɛ jieɔ lɛ baa shi kwraa fe F-Con kɛ F-BLG-treated colonic epithelial 8B).Nɛkɛ saji nɛɛ tsɔɔ akɛ BLG helatsamɔ lɛ ha SCFA-ni jɛɔ GLP-1 mli lɛ sɛɛ foɔ jogbaŋŋ.
SCFA ni jɛ BLG mli lɛ haa GLP-1 jeɔ kpo kɛjɛɔ shishijee tsɛŋemɔ hela mli wala yibii lɛ amli.(A) Acetic acid, propionic acid, kɛ butyric acid haa GLP-1 jeɔ kpo kɛjɛɔ shishijee tsɛŋemɔ hela mli wala yibii lɛ amli; (B) F-Con, F-DSS kɛ F-BLG tsirɛɔ shishijee tsɛŋemɔ helai ni yɔɔ tsɛŋemɔ hela mli lɛ GLP-1 ni ajieɔ lɛ kpo lɛ. F-BLG (ni kɛ 0.25 g feces yeɔ egbɔ), yɛ gbɛ kome nɔ. 2 ŋmɛlɛtswai yɛ 37°C, 5% CO2, yɛ gbɛ kome nɔ. GLP-1 ni ajieɔ kɛjɛɔ shishijee murine colonic epithelial wala yibii lɛ amli lɛ ji nɔ ni ELISA na. *p < 0.05 kɛ F-DSS.
Wiemɔi kukuji: Ace, asetik asid; Pro, propiyonik asid; shi kɛlɛ, butyric asid; F-Con, ni ji ŋmeii ni ajieɔ kɛjɛɔ ŋmeii ni akudɔ amɛ lɛ amli; F-DSS, ni ji ŋmɔtɔ ni ajieɔ kɛjɛɔ ŋmɔtɔ mli; F-BLG, kɛjɛ BLG-ni akɛtsaa tsɛŋemɔ hela mli Fecal ni ajieɔ kɛjɛɔ tsɛŋemɔ hela mli.
Akɛni Jeŋ Hewalɛ He Gbɛjianɔtoo lɛ etsɔɔ akɛ hela ko ni anyɛɛɛ atsa hewɔ lɛ, UC miibafee jeŋ muu fɛɛ oshara; Shi kɛlɛ, gbɛi ni mɔɔ shi jogbaŋŋ ni atsɔɔ nɔ atsɔɔ hela lɛ hiɛ, atsĩɔ naa, ni atsaa lɛ faaa lolo. No hewɔ lɛ, ehe miihia ni atao ni afee tsofafeemɔ gbɛi heei ni yɔɔ shweshweeshwe ni tsuɔ nii jogbaŋŋ kɛha UC. ni amɛ fɛɛ amɛji nibii ni wala yɔɔ mli kɛ adebɔɔ mli nibii ni fe fɛɛ lɛ, amɛyeee adesai kɛ kooloi awui.31,32 Nikasemɔ nɛɛ yiŋtoo ji ni atao Chinese tsofafeemɔ he gbɛjianɔtoo ko ni yɔɔ shweshweeshwe ni tsuɔ nii jogbaŋŋ kɛha UC tsamɔ ni akwɛ bɔ ni etsuɔ ​​nii eha lɛ mli.BLG ji Chinese tsofafeemɔ tsofa ko ni ale jogbaŋŋ ni akɛtsuɔ nii kɛtsaa flufla lɛ yɛ wɔ Workory3 lɛ mli. indigo, ni ji Chinese tsofafeemɔ mli tsofa ko ni afee kɛjɛ nibii ni akɛfee BLG lɛ nɔŋŋ mli lɛ, jieɔ bɔ ni etsuɔ ​​nii jogbaŋŋ ehaa yɛ UC helatsamɔ mli yɛ gbɔmɛi kɛ kooloi amli lɛ kpo.4,34 Shi kɛlɛ, BLG kɛ esɛɛnamɔi ni teɔ shi ewoɔ hela ni haa mɔ he jɔ̃ɔ ehe lɛ he hewalɛ ni eyɔɔ lɛ gbɛ ni atsɔɔ nɔ atsuɔ he nii lɛ mli kãaa shi faŋŋ. fũu, ni kɛ gut microbiota lɛ tsakemɔ kɛ gut-derived GLP-1 ni afeɔ lɛ ekoŋŋ lɛ baa.
Ale jogbaŋŋ akɛ UC lɛ ji bei ni sɛɛ tsɛɔ ni helatsamɔhe lɛ mli nibii ni afɔɔ namɔ yɔɔ mli, tamɔ shwiili mli shwiili, shwiemɔ, lá ni hoɔ yɛ fɔmɔ kotoku mli, kɛ fɔmɔ kotoku mli fãji ni fiteɔ babaoo lɛ. nu. Taakɛ atsɔɔ yɛ mfoniri 1B lɛ mli lɛ, shwiili ni tsakeɔ kɛ DAI yibɔi lɛ tsɔɔ omanyeyeli ni jɛɔ hela ni haa mɔ he jɔ̃ɔ ehe ni sɛɛ tsɛɔ lɛ mli baa lɛ mli. colitis.Yɛ tsɛŋemɔ hela kɛ tsɛŋemɔ hela he lɛ, tsɛŋemɔ hela lɛ sɛɛ tsɛɔ, tsɛŋemɔ hela lɛ mli fãji ni fiteɔ, kɛ tsɛŋemɔ hela ni haa mɔ mli fũuɔ lɛ mli nibii ni haa mɔ mli fũuɔ lɛ TNF-α, IL-1β, kɛ IL-6 ni yɔɔ tsɛŋemɔ hela mli lɛ afeemɔ hu tee hiɛ waa yɛ BLG helatsamɔ sɛɛ. kwakei.
Te BLG tsuɔ etsofafeemɔ he hewalɛi lɛ ahe nii ehaa tɛŋŋ?Nikasemɔi babaoo ni eho lɛ etsɔɔ akɛ, gut microbiota lɛ tsuɔ gbɛfaŋnɔ titri ko he nii yɛ UC helai lɛ amli, ni tsofai ni damɔ microbiome nɔ kɛ microbiome-targeted therapies lɛ eba akɛ gbɛ ni ŋɔɔ waa kɛha UC tsamɔ,we ŋmɛnɛŋmɛnɛ nikasemɔ lɛ jie nɔ ni jɛ mli ba lɛ kpo. tsakemɔi yɛ gut microbiota mli nibii amli, ni tsɔɔ akɛ BLG ni buɔ mɔ he kɛjɛɔ DSS-ni kɛ colitis baa lɛ he lɛ kɛ gut microbiota lɛ tsakemɔ yɔɔ tsakpaa. strictly anaerobic bacteria ni hiɔ fɔmɔ kotoku lɛ mli, ni fiteɔ fɔmɔ kotoku lɛ, ejieɔ propionic acid, ehaa goblet cell lɛ feɔ srɔto, ni ekwɛɔ fɔmɔ kotoku lɛ nɔ. nitsumɔ ni kɔɔ gbɛtsii nii ni tsiɔ mɔ naa lɛ he.26 Helatsamɔhe kɛ kooloi ahe saji babaoo tsɔɔ akɛ Akkermansia kɛ mucosa ni yɔɔ hewalɛ,38 kɛ Akkermansia spp. Wɔ saji ni wɔyɔɔ amrɔ nɛɛ tsɔɔ akɛ, Akkermansia ni fa babaoo lɛ yaa hiɛ waa yɛ BLG helatsamɔ sɛɛ. Kɛfata he lɛ, Prevotellaceae_UCG-001 ji SCFA-feemɔ hela ko. 40,41 Wɔ ŋmɛnɛŋmɛnɛ saji lɛ hu tsɔɔ akɛ BLG helatsamɔ baanyɛ aha Prevotellaceae_UCG-001 ni fa babaoo yɛ DSS-tsamɔ ŋmeii lɛ amli lɛ aya hiɛ waa. UC mice ni ekɛ IL-6 kɛ IL-1β ŋwɛi gbɛhei kɛ helai ahe yibɔi lɛ yeɔ tsakpaa jogbaŋŋ. 45,46 Wɔ ŋmɛnɛŋmɛnɛ saji lɛ hu tsɔɔ akɛ SCFA acetate, propionate, kɛ butyrate ni yɔɔ DSS-ni akɛtsaa fɔmɔ kotokui lɛ amli lɛ tee hiɛ waa yɛ BLG-ni akɛtsaa fɔmɔ kotokui lɛ amli lɛ mli faŋŋ akɛ, ehaa DSS-ni haa SCFA-feɔ bacteria lɛ yaa hiɛ jogbaŋŋ yɛ ŋmeii ni yɔɔ tsɛŋemɔ hela ni haa mɔ he jɔ̃ɔ ehe ni sɛɛ tsɛɔ lɛ mli.
GLP-1 ji incretin ni ajieɔ lɛ kpo titri yɛ ileum kɛ colon mli ni etsuɔ ​​gbɛfaŋnɔ ko ni he hiaa waa yɛ fɔmɔ kotoku lɛ mli nibii ni shwieɔ shi lɛ mli, ni ehaa lá mli glucose ni baa shi yɛ niyenii sɛɛ lɛ baa shi. ni abɔ he amaniɛ yɛ nikasemɔi ni eho lɛ amli lɛ, SCFA ni fa babaoo lɛ kɛ plasma GLP-1 ni yɔɔ adesai kɛ ŋmeii amli lɛ yeɔ tsakpaa. 52 Wɔ amrɔ nɛɛ saji lɛ tsɔɔ akɛ, yɛ BLG helatsamɔ sɛɛ lɛ, serum GLP-1 lɛ mlijaa kɛ Gcg mRNA kpojiemɔ lɛ tee hiɛ waa. tsɔɔ GLP-1 lɛ kpojiemɔ lɛ nɔ hewalɛ?Gwen Tolhurst kɛ ekrokomɛi. SCFA baanyɛ aha GLP-1 ajie ehe kpo kɛtsɔ GRP43 kɛ GPR41.29 Wɔ ŋmɛnɛŋmɛnɛ saji lɛ hu tsɔɔ akɛ BLG helatsamɔ haa mRNA ni ajieɔ lɛ kpo yɛ GRP43 kɛ GPR41 mli lɛ yaa hiɛ waa yɛ DSS-tsamɔ ŋmeii lɛ amli.
BLG ji tsofa ko ni akɛtsuɔ nii be kakadaŋŋ yɛ China. Amrɔ nɛɛ, BLG (ni sugar bɛ mli) ni akɛwoɔ gbɔmɔ mli lɛ falɛ ni atsɔɔ akɛ akɛhaa lɛ ji 9-15 g/gbi (shii etɛ yɛ gbi kome mli).Wɔ nikasemɔ lɛ tsɔɔ akɛ ameliiduated DBLG/K Nɛkɛ tsofa nɛɛ bɛŋkɛ BLG tsofa ni akɛtsuɔ nii yɛ helatsamɔhe lɛ. Wɔ nikasemɔ lɛ hu na akɛ gbɛ ni etsɔɔ nɔ etsuɔ ​​nii lɛ ji nɔ ni tsɔɔ tsakemɔi ni baa yɛ fɔmɔ kotoku mli nibii bibii ni wala yɔɔ mli lɛ amli, titri lɛ SCFA-ni feɔ fɔmɔ kotoku mli helai, tamɔ Gkermansia_UCGoreceae1, tamɔ Gkermansia_UCGoreceae1. Shi kɛlɛ, gbɛ pɔtɛɛ ni etsɔɔ nɔ etsakeɔ gut microbiota lɛ kã he eji nɔ ni esa akɛ asusu he jogbaŋŋ kɛtsɔ BLG nɔ akɛ tsofafeemɔ gbɛ ni baanyɛ atsu nii kɛha helatsamɔhe mli hela ni haa mɔ he jɔ̃ɔ ehe lɛ.
Ace, asetik asid; shi, butirik asidi; BLG, ŋmei; DSS, ni ji tsofa ni haa mɔ he jɔɔ lɛ; DAI, hela nitsumɔ he okadi; DPP, ni ji tsofa ni haa mɔ he jɔɔ lɛ; FID, la ni tsoɔ ni haa anaa; F-Con, ni ji Fecal ni ajieɔ kɛjɛɔ ŋmeii amli lɛ nɔkwɛmɔ; F-DSS, ni ji DSS hela ni haa mɔ he jɔ̃ɔ ehe lɛ mli nu ni ajieɔ kɛjɛɔ mli; F-BLG, ni ji BLG ni akɛtsaa tsɛŋemɔ hela ni haa mɔ he jɔ̃ɔ ehe lɛ mli nu ni ajieɔ kɛjɛɔ mli; GLP-1, ni ji tsofa ko ni tamɔ glukagon-1; Gcg, glukagon; gas kromatograf, gas kromatograf; GRP43, G ni akɛ tsofa ni haa mɔ he waa lɛ feɔ ekome lɛ 43; GRP41, G nibii ni haa mɔ he jɔɔ lɛ 41; H&E, lá ni haa mɔ he jɔɔ lɛ; HBSS, Hanks Ŋmei ni Akɛtoɔ He lɛ ; OTC, OTC; PCA, nibii titrii ni yɔɔ mli lɛ amlipɛimɔ; PCoA, gbɛjianɔtoo titri mlipɛimɔ; Pro, propiyonik asid; SASP, tsofa ni haa mɔ tsui nyɔɔ emli; SCFA, ni ji tsofa ni haa mɔ he jɔɔ lɛ kuku; Chinese tsofafeemɔ, Chinese kusum tsofafeemɔ; UC, hela ni haa mɔ mli fũuɔ.
Nibii ni akwɛɔ mli lɛ fɛɛ ji nɔ ni Peking Yunivɛsiti Shenzhen-Hong Kong Yunivɛsiti ni Kwɛɔ Jeŋ Nilee kɛ Teknɔlɔji Tsofafeemɔ He (Shenzhen, China) lɛ kpɛlɛ nɔ yɛ gbɛtsɔɔmɔi kɛ kooloi ahe mlai (jeŋba yibɔ A2020157) lɛ naa.
Niŋmalɔi lɛ fɛɛ ye amɛbua waa yɛ susumɔ kɛ gbɛjianɔtoo, saji ni ana, loo saji amlipɛimɔ kɛ shishitsɔɔmɔ mli; ekɛ ehe wo niŋmaa lɛ ŋmalɛ mli loo nilee mli saji ni he hiaa lɛ amlipɛimɔ mli jogbaŋŋ; ekpɛlɛ nɔ akɛ ekɛ wolo ni akɛ niji ŋmala lɛ baaha wolo tɛtrɛɛ ni yɔɔ amrɔ nɛɛ; naagbee lɛ, ekpɛlɛ shishitsɔɔmɔ lɛ nɔ koni ajie lɛ kpo; Nitsumɔ lɛ fãi fɛɛ ahe sɔ̃ kã enɔ.
Nitsumɔ nɛɛ ji nɔ ni China maŋ adebɔɔ mli nibii ahe nilee shishitoo lɛ (81560676 kɛ 81660479), Shenzhen Yunivɛsiti lɛ klɛŋklɛŋ klas nitsumɔ lɛ (86000000210), Shenzhen Jeŋ Nilee kɛ Teknoloji Hee Ajinafoi Akuu lɛ Shika (JCYJ202103240938100) fi sɛɛ. Nibii amlitaomɔ shika (A2020157 kɛ A2020272), Guizhou Tsofafeemɔ He Nikasemɔhe lɛ Tsofafeemɔ He Guizhou Kpokpaa lɛ ni Key Laboratory (YWZJ2020-01) kɛ Peking Yunivɛsiti Shenzhen Helatsamɔhe lɛ (JCYJ2018009) kɛ shika ha.
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