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Hoʻopau nā granules Ban-Lan-Gen i ka dextran sodium sulfate-induced chronic relapsing colitis i nā ʻiole ma o ka hoʻololi ʻana i ka microbiota gut a me ka hoʻihoʻi ʻana i ka hana ʻana o ka intestinal SCFA Derived-GLP-1.
ʻO 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 Haitao21 Ke Kulanui ʻo Peking Ke Keʻena Hoʻōla Lāʻau Lapaʻau o Shenzhen, Shenzhen, Repubalika o Kina; 2 Ke Kikowaena ʻEpekema Ola o ke Kulanui ʻo Shenzhen Kula o ka Hoʻōla Lāʻau Lapaʻau, Shenzhen, Repubalika o Kina; 3 Ke Kulanui Lapaʻau ʻo Guizhou Ke Kikowaena Noiʻi ʻenehana ʻenekinia no ka lāʻau lapaʻau lāhui a me ka hoʻomohala ʻana a me ka noi ʻana o ka lāʻau lapaʻau kuʻuna Kina Ke Keʻena Hoʻonaʻauao, Keʻena Hoʻokolohua Koʻikoʻi o ka Lāʻau Lapaʻau o ka Panalāʻau ʻo Guizhou, Guiyang, Repubalika o Kina; 4 Keʻena Gastroenterology, Ke Kulanui ʻo Peking Keʻena Hoʻōla Lāʻau Lapaʻau o Shenzhen, Shenzhen, Repubalika o Kina; 5 Kula o ka Hoʻōla Lāʻau Lapaʻau, Ke Kulanui Lapaʻau ʻo Guizhou, Keʻena Hoʻokolohua Koʻikoʻi o ka Mokuʻāina no ka Hana a me ka Noi ʻana o nā Mea Lapaʻau, Guiyang; 6 Keʻena o ka Lapaʻau Lapaʻau, Halemai ʻo Peking University Shenzhen, Shenzhen, Kina [email protected] Shen Xiangchun, Kula o ka Hale Lapaʻau, Guizhou Medical University, Guizhou, People's Republic of China, 550004, Leka uila [email protected] Pahuhopu: ʻO ka lāʻau lapaʻau e pili ana i ka GLP-1 kahi koho lapaʻau hou no ka maʻi ʻōpū mumū. ʻO nā granules Ban-Lan-Gen (BLG) kahi ʻano hana antiviral TCM i ʻike ʻia e hōʻike ana i ka hana anti-inflammatory hiki ke mālama i nā ʻano maʻi like ʻole. Eia nō naʻe, ʻaʻole maopopo loa kona hopena anti-inflammatory ma ka colitis a me kāna ʻano hana. NĀ ʻANO: No ka hoʻokumu ʻana i ka dextran sodium sulfate (DSS)-induced chronic relapsing colitis i nā ʻiole. Ua hana ʻia nā ʻōkuhi hana maʻi, nā māka histological o ka hōʻeha, a me nā pae cytokine proinflammatory e loiloi i ka hopena pale o BLG. Ua hōʻike ʻia nā hopena o BLG ma ka microbiota ʻōpū a me ka ʻōpū e nā pae serum GLP-1 a me ka colonic Gcg, GPR41, a me ka hōʻike ʻana o GRP43, ka haku mele ʻana o ka microbiota ʻōpū, nā pae SCFA fecal, a Hoʻokuʻu ʻia ʻo GLP-1 mai nā pūnaewele epithelial colonic mua o ka ʻiole SCFA i loaʻa mai ka hana GLP-1. Nā hopena: Ua hōʻemi nui ka mālama ʻana o BLG i ka pohō kaumaha o ke kino, DAI, ka pōkole ʻana o ka colon, ka hōʻino ʻana o nā ʻiʻo colon, a me nā pae cytokine proinflammatory o TNF-α, IL-1β, a me IL-6 i loko o nā ʻiʻo colon. Eia kekahi, hiki i ka mālama ʻana o BLG ke hoʻihoʻi nui i ka colonic Gcg, GPR41 a me GRP43 expression a me nā pae serum GLP-1 i nā ʻiole colitis, a ma ka hoʻonui ʻana i nā bacteria hana SCFA e like me Akkermansia a me Prevotellaceae_UCG-001, a me ka hoʻemi ʻana i ka nui o nā bacteria e like me Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas a me Oscillibacter. Eia kekahi, hiki i ka mālama ʻana o BLG ke hoʻonui nui i ka pae o SCFAs i loko o nā feces o nā ʻiole colitis. I ka manawa like, ua hōʻike pū nā hoʻokolohua in vitro e hiki i ka ʻāpana fecal o nā ʻiole i mālama ʻia e BLG ke hoʻoulu nui i nā pūnaewele epithelial colonic Murine liʻiliʻi mua e huna iā GLP-1. Nā hopena: Hōʻike kēia mau ʻike he hopena anti-colitis ko BLG. Loaʻa iā BLG ka hiki ke hoʻomohala ʻia ma ke ʻano he lāʻau lapaʻau, ma ka liʻiliʻi ma ka hoʻololi ʻana i ka microbiota gut a me ka hoʻihoʻi ʻana i ka hana ʻana o GLP-1 i loaʻa mai ka SCFA i loko o ka ʻōpū. Nā lāʻau lapaʻau hoʻohiki no ka colitis relapsing mau. Nā huaʻōlelo koʻikoʻi: colitis, nā granules Ban-Lan-Gen, ka microbiota gut, nā waikawa momona kaulahao pōkole, GLP-1
ʻO ka Ulcerative colitis (UC) kahi maʻi mumū lōʻihi o ka colon a me ka rectum i hōʻike ʻia e ka maʻi diarrhea hou, ka ʻeha o ka ʻōpū, ka pohō kaumaha, a me nā ʻōpala koko mucopurulent.1 I kēia manawa, ua piʻi ka nui o ka UC ma nā ʻāina i emi mua ka hanana, me Kina, me ka piʻi ʻana o ke kaulana o nā nohona Komohana.2 Ke hoʻopilikia nei kēia hoʻonui i nā pilikia nui no ke olakino lehulehu a he hopena koʻikoʻi no ka hiki o nā mea maʻi ke hana a me ke ʻano o ke ola. ʻO ka mea nui, ʻaʻole maopopo loa ka pathogenesis o UC, akā ua ʻae ʻia he mea kōkua ka genetics, nā mea pili i ke kaiapuni, ka microbiota gut, a me ka ʻōnaehana pale i ka hoʻomohala ʻana o UC.3 I kēia manawa, ʻaʻohe lāʻau lapaʻau no UC, a ʻo ka pahuhopu o ka lāʻau lapaʻau, ʻo ia ke kāohi ʻana i nā hōʻailona lapaʻau, hoʻoulu a mālama i ke kala ʻana, hoʻolaha i ka ho'ōla mucosal, a hōʻemi i ka hoʻi hou ʻana. ʻO nā lāʻau lapaʻau kuʻuna e pili ana i nā aminosalicylates, corticosteroids, immunosuppressants, a me biologics. Eia naʻe, ʻaʻole hiki i kēia mau lāʻau ke hoʻokō i ka hopena i makemake ʻia ma muli o kā lākou mau hopena ʻaoʻao like ʻole.4 I kēia manawa, ua hōʻike nā haʻawina hihia he nui ua hōʻike ka lāʻau lapaʻau kuʻuna Kina (TCM) i ka hiki ke kōkua i ka hōʻoluʻolu ʻana i ka UC me ka haʻahaʻa haʻahaʻa, e hōʻike ana ʻo ka hoʻomohala ʻana o nā lāʻau lapaʻau TCM hou he hoʻolālā lapaʻau hoʻohiki no UC.5-7
ʻO Banlangen Granules (BLG) kahi lāʻau lapaʻau kuʻuna Kina i hana ʻia mai ka wai o ke aʻa Banlangen.8 Ma waho aʻe o kona hopena antiviral, hōʻike ʻo BLG i ka hana anti-inflammatory hiki ke mālama i nā ʻano maʻi like ʻole.9,10 Eia kekahi, ua hoʻokaʻawale ʻia nā glucosinolates (R,S-goitrin, progoitrin, epiprorubin a me glucoside a ua ʻike ʻia mai nā wai o Radix isatidis) a me nā nucleosides (hypoxanthine, adenosine, uridine a me guanosine) a me nā alkaloids indigo e like me indigo a me indirubin.11,12 Ua hoʻopaʻa maikaʻi ʻia nā haʻawina mua e hōʻike ana nā hui adenosine, uridine a me indirubin i nā hopena anti-colitis ikaika i nā ʻano holoholona like ʻole o ka colitis.13-17 Eia naʻe, ʻaʻohe haʻawina i hoʻokumu ʻia i nā hōʻike e loiloi i ka pono o BLG i ka colitis.I loko o ke aʻo ʻana o kēia manawa, ua noiʻi mākou i ka hopena pale o BLG ma ka dextran sodium sulfate (DSS)-induced chronic relapsing colitis ma nā ʻiole C57BL/6 a ua loaʻa. ʻo ka lawelawe waha ʻana o BLG i hoʻonāwaliwali nui i ka colon relapsing mau i hoʻokomo ʻia e DSS i nā ʻiole, ʻo kāna mau hana hoʻoponopono e pili ana me ka modulation o ka microbiota gut a me ka hoʻihoʻi ʻana i ka hana glucagon-like peptide-1 (GLP-1) i loaʻa mai i ka ʻōpū.
ʻO nā granules BLG (ʻaʻohe kō, NMPA-approved Z11020357; Beijing Tongrentang Technology Development Co., Ltd., Beijing, Kina; helu pūʻulu: 20110966) ua kūʻai ʻia mai nā hale kūʻai lāʻau lapaʻau. Ua kūʻai ʻia ʻo DSS (Molecular Weight: 36,000–50,000 Daltons) mai MP Biologicals (Santa Ana, USA). Ua kūʻai ʻia ʻo Sulfasalazine (SASP) (≥ 98% maʻemaʻe), hematoxylin a me eosin mai Sigma-Aldrich (St. Louis, MO, USA). Ua kūʻai ʻia nā kime assay Mouse TNF-α, IL-1β a me IL-6 luminex Elisa mai nā ʻōnaehana R&D (Minneapolis, MN, USA). Ua kūʻai ʻia ka waikawa acetic, ka waikawa propionic, a me ka waikawa butyric mai Aladdin Industries (Shanghai, Kina). Ua kūʻai ʻia ka waikawa 2-Ethylbutyric mai Merck KGaA (Darmstadt, Kelemānia).
Ua kūʻai ʻia nā ʻiole kāne C57BL/6 he 6-8 pule (ke kaumaha o ke kino he 18-22 g) mai Beijing Wetahe Laboratory Animal Technology Co., Ltd. (Beijing, Kina) a ua hoʻonoho ʻia i loko o kahi ʻano o 22 ± 2 °C me 12 h pōʻaiapuni mālamalama/pōʻeleʻele. Ua hānai ʻia nā ʻiole i kahi meaʻai rodent maʻamau me ke komo manuahi ʻana i ka wai inu no hoʻokahi pule e hoʻomaʻamaʻa ai i ke kaiapuni hou. A laila ua māhele ʻia nā ʻiole i ʻehā mau pūʻulu: ka hui hoʻomalu, ka hui hoʻohālike DSS, ka hui i mālama ʻia me SASP (200 mg/kg, waha) a me ka hui i mālama ʻia me BLG (1 g/kg, waha). E like me ka mea i hōʻike ʻia ma ke Kiʻi 1A, e like me kā mākou noiʻi mua, ua hoʻoulu ʻia ka colitis relapsing mau hoʻokolohua i loko o nā ʻiole e ʻekolu mau pōʻaiapuni o 1.8% DSS no 5 mau lā, a ukali ʻia e ka wai i hoʻoheheʻe ʻia no 7 mau lā, e like me kā mākou noiʻi mua.18 Ua mālama ʻia nā ʻiole ma nā hui i mālama ʻia me SASP a me BLG me SASP a me BLG, i kēlā me kēia lā e hoʻomaka ana mai ka lā 0. Wahi a nā hoʻokolohua mua, ʻo ka Ua hoʻonohonoho ʻia ka nui o BLG ma 1 g/kg. I kēia manawa, ua hoʻonohonoho ʻia ka nui o SASP ma 200 mg/Kg e like me ka palapala.4 Ua loaʻa i nā hui hoʻohālike kaohi a me DSS ka nui like o ka wai ma o ka hoʻokolohua.
Kiʻi 1 Hoʻomaikaʻi ʻo BLG i ka colitis relapsing mau i hoʻokomo ʻia e DSS i nā ʻiole. (A) Hoʻolālā hoʻokolohua o ka colitis recurrent mau a me ka mālama ʻana, (B) loli kaumaha o ke kino, (C) helu helu kuhikuhi hana maʻi (DAI), (D) lōʻihi o ke kolona, ​​(E) kiʻi hōʻike o ke kolona, ​​(F) H&E staining Colon (magnification, ×100) a me (G) helu histological. Hōʻike ʻia nā ʻikepili ma ke ʻano he awelika ± SEM (n = 6).##p < 0.01 a i ʻole ###p < 0.001 vs ka hui kaohi (Con); *p < 0.05 a i ʻole **p < 0.01 a i ʻole ***p < 0.001 vs hui DSS.
Ua hoʻopaʻa ʻia ke kaumaha o ke kino, ke kūlike o ka ʻōpala, a me ke kahe ʻana o ke koko i kēlā me kēia lā. Ua hoʻoholo ʻia ka helu hana maʻi (DAI) ma ka hoʻohui ʻana i nā helu o ke kaumaha o ke kino, ke kūlike o ka ʻōpala, a me ke kahe ʻana o ke koko i ka rectal e like me ka mea i wehewehe mua ʻia.19 I ka hopena o ka hoʻokolohua, ua pepehi ʻia nā ʻiole a pau a ua hōʻiliʻili ʻia ke koko, nā ʻōpala a me ka colon no nā hoʻokolohua hou aku.
Ua hoʻopaʻa ʻia ka ʻiʻo kolona me ka formalin a ua hoʻokomo ʻia i loko o ka paraffin. Ua hana ʻia nā ʻāpana 5-micron a ua hoʻoluʻu ʻia me ka hematoxylin-eosin (H&E), a laila ua makapō ʻia a helu ʻia e like me ka mea i wehewehe mua ʻia.19
Ua unuhi ʻia ka RNA holoʻokoʻa o ka ʻiʻo colon e ka Trizol reagent (Invitrogen, Carlsbad, CA), a ukali ʻia e ka unuhi cDNA me ka reverse transcriptase (TaKaRa, Kusatsu, Shiga, Iapana). Ua hana ʻia ka PCR Quantitative me ka hoʻohana ʻana i kahi ʻōnaehana PCR manawa maoli me SYBR Green Master (Roche, Basel, Switzerland). Ua hoʻonohonoho ʻia nā transcripts gene target i β-actin a ua kālailai ʻia nā ʻikepili me ka hoʻohana ʻana i ke ʻano 2-ΔΔCT. Hōʻike ʻia nā moʻo primer gene ma ka Papa 1.
Ua hana ʻia ka hoʻokaʻawale ʻana a me ka moʻomeheu ʻana o nā ʻiole colonic epithelial cell e like me ka mea i wehewehe mua ʻia.20 I ka pōkole, ua ʻoki mua ʻia nā colons o nā ʻiole 6-8 pule ma hope o ka mōhai ʻana e ka dislocation cervical, a laila wehe ʻia i ka longitudinally, mālama ʻia me Hanks Balanced Salt Solution (HBSS, me ka ʻole o ka calcium a me ka magnesium) a ʻokiʻoki ʻia i loko o 0.5-1 mm o nā ʻāpana liʻiliʻi. Ma hope mai, ua ʻeli ʻia nā ʻiʻo me 0.4 mg/mL collagenase XI (Sigma, Poole, UK) i loko o ka medium DMEM manuahi a centrifuged ma 300 xg no 5 min ma ka mahana o ka lumi. Hoʻokuʻu hou i ka pellet i loko o ka medium DMEM (i hoʻohui ʻia me 10% fetal bovine serum, 100 Units/mL penicillin, a me 100 µg/mL streptomycin) ma 37 °C a hele ma waena o kahi nylon mesh (ka nui o ka pore ~250 µm). Ua kau ʻia nā Aliquots o nā ʻiole epithelial colonic i loko o nā kīʻaha lalo aniani a hoʻoulu ʻia me ka acetic acid, propionic acid, butyric acid, a me ka fecal mouse. nā mea i hoʻokaʻawale ʻia no 2 mau hola ma 37°C, 5% CO2.
Ua hoʻohuihui ʻia nā ʻiʻo kolona me PBS, a ua ʻike ʻia nā pae o nā cytokines IL-6, TNF-α a me IL-1β i loko o nā ʻiʻo kolona me ka hoʻohana ʻana i nā luminex ELISA assay kits (nā ʻōnaehana R&D, Minneapolis, MN, USA). Pēlā nō, ua hoʻoholo ʻia nā pae GLP-1 i loko o ka serum a me ka culture medium o nā cell epithelial kolona murine mua me kahi pahu ELISA (Bioswamp, Wuhan, Kina) e like me nā kuhikuhi a ka mea hana.
Ua unuhi ʻia ka DNA holoʻokoʻa mai nā feces me ka hoʻohana ʻana i kahi pahu unuhi DNA (Tiangen, Kina). Ua ana ʻia ke ʻano a me ka nui o ka DNA ma nā lakio o 260 nm/280 nm a me 260 nm/230 nm, kēlā me kēia. Ma hope mai, me ka hoʻohana ʻana i kēlā me kēia DNA i unuhi ʻia ma ke ʻano he template, ua hoʻohana ʻia nā primers kikoʻī 338F (ACTCCTACGGGAGGCAGCAG) a me 806R (GGACTACHVGGGTWTCTAAT) e hoʻonui i nā ʻāpana V3-V4 o ka gene 16S rRNA ma nā ʻāpana like ʻole. Ua hoʻomaʻemaʻe ʻia nā huahana PCR me ka hoʻohana ʻana i ka QIAquick Gel Extraction Kit (QIAGEN, Kelemānia), i helu ʻia e ka PCR manawa maoli, a ua hoʻonohonoho ʻia me ka hoʻohana ʻana i ka paepae hoʻonohonoho IlluminaMiseq PE300 (Illumina Inc., CA, USA). No ka nānā ʻana i ka bioinformatics, ua hana ʻia ka hana ʻikepili ma hope o nā protocols i hōʻike mua ʻia.21,22 I ka pōkole, e hoʻohana iā Cutadapt (V1.9.1) e kānana i nā faila express maka. Ua hui pū ʻia nā OTU me ka hoʻohana ʻana iā UPARSE (mana 7.0.1001) me kahi ʻoki like o 97%, a ua hoʻohana ʻia ʻo UCHIME e wehe i nā moʻo chimeric. Ua hana ʻia ka loiloi haku mele kaiāulu a me ka hoʻokaʻawale ʻana me ka hoʻohana ʻana i ka mea hoʻokaʻawale RDP (http://rdp.cme.msu.edu/) ma muli o ka waihona ʻikepili gene SILVA ribosomal RNA.
Ua ana ʻia nā pae o nā waikawa momona kaulahao pōkole (ʻakika acetic, waikawa propionic, a me ka waikawa butyric) e like me ka mea i wehewehe mua ʻia e Tao et al., me kekahi mau hoʻololi.23 I ka pōkole, ua hoʻokuʻu mua ʻia he 100 mg o nā feces i loko o 0.4 mL o ka wai deionized, a ukali ʻia e 0.1 mL o 50% sulfuric acid a me 0.5 mL o 2-ethylbutyric acid (kūlana kūloko), a laila homogenized a hoʻomehana ʻia ma 4°C. Centrifuge ma 12,000 rpm no 15 mau minuke ma C. Ua unuhi ʻia ka supernatant me 0.5 mL o ka ether a ua hoʻokomo ʻia i loko o ka GC no ka nānā ʻana. No ka nānā ʻana i ka chromatography gas (GC), ua nānā ʻia nā laʻana me ka hoʻohana ʻana i kahi chromatograph gas GC-2010 Plus (Shimadzu, Inc.) i lako me kahi mea ʻike ionization lapalapa (FID). Ua hoʻokō ʻia ka hoʻokaʻawale ʻana me ka hoʻohana ʻana i kahi kolamu ZKAT-624, 30 m × 0.53 mm × 0.3 μm (Lanzhou Zhongke Antai Analytical Technology Co., Ltd., Kina). Ua loaʻa nā ʻikepili me ka hoʻohana ʻana i ka polokalamu hoʻonā GC (Shimadzu, Inc.). ʻO ka lakio māhele he 10: 1, ʻo ke kinoea lawe he nitrogen, a ʻo ka nui o ke kahe he 6 mL/min. ʻO ka nui o ka injection he 1 μL. ʻO ka mahana o ka injector a me ka mea ʻike he 300°C. Ua mālama ʻia ka mahana o ka umu ma 140°C no 13.5 mau minuke, a laila hoʻonui ʻia i 250°C ma ka wikiwiki o 120°C/min; ua paʻa ka mahana no 5 mau minuke.
Hōʻike ʻia nā ʻikepili ma ke ʻano he awelika ± hewa maʻamau o ka awelika (SEM). Ua loiloi ʻia ke koʻikoʻi o ka ʻikepili e ka ANOVA hoʻokahi ala a ukali ʻia e ka hoʻāʻo laulā lehulehu a Duncan. Ua hoʻohana ʻia ka polokalamu GraphPad Prism 5.0 (GraphPad Software Inc., San Diego, CA, USA) no nā helu āpau a ua manaʻo ʻia ʻo p < 0.05 he koʻikoʻi ma ka helu helu.
Ua ʻike maopopo ʻia ʻo UC kahi maʻi colitis relapsing mau loa me ka ʻeha nui o ka ʻōpū, ka maʻi diarrhea a me ke kahe ʻana o ke koko. No laila, ua hoʻokumu ʻia ka colitis relapsing mau loa i hoʻokomo ʻia e DSS i nā ʻiole e loiloi i ka pono anti-colitis o BLG (Kiʻi 1A). Ke hoʻohālikelike ʻia me ka hui kaohi, ua emi nui ke kaumaha o ke kino o nā ʻiole ma ka hui hoʻohālike DSS a me ka DAI kiʻekiʻe, a ua hoʻohuli nui ʻia kēia mau hoʻololi ma hope o 24 mau lā o ka mālama ʻana iā BLG (Kiʻi 1B a me C). ʻO ka pōkole ʻana o Colon kahi hōʻailona koʻikoʻi o UC. E like me ka mea i hōʻike ʻia ma nā Kiʻi 1D a me E, ua pōkole nui ʻia ka lōʻihi o ka colon o nā ʻiole i loaʻa iā DSS, akā ua hoʻomaha ʻia e ka mālama ʻana iā BLG. Ma hope mai, ua hana ʻia ka nānā ʻana o ka histopathological e loiloi i ka mumū o ka colon. Ua hōʻike nā kiʻi i hoʻoluʻu ʻia e H&E a me nā helu pathological ua hoʻopilikia nui ka hoʻokele DSS i ka hoʻolālā colonic a ua hopena i ka luku ʻana o ka crypt, ʻoiai ua hōʻemi nui ka mālama ʻana iā BLG i ka luku ʻana o ka crypt a me nā helu pathological (Kiʻi 1F a me G). ʻO ka mea nui, ʻo ka hopena pale o BLG ma kahi mahele o 1 g/Kg ua like ia me ka SASP ma he mahele o 200 mg/Kg. Ma ke ʻano hui, hōʻike kēia mau ʻike he pono ka BLG i ka hōʻemi ʻana i ke koʻikoʻi o ka colitis relapsing mau i hoʻokomo ʻia e DSS i nā ʻiole.
ʻO TNF-α, IL-1β a me IL-6 nā māka mumū koʻikoʻi o ka mumū o ka colonic. E like me ka mea i hōʻike ʻia ma ke Kiʻi 2A, ua hoʻoulu ʻo DSS i kahi piʻi nui o ka hōʻike ʻana o ka gene o TNF-α, IL-1β a me IL-6 i loko o ka colon i hoʻohālikelike ʻia me ka hui kaohi. Hiki i ka hoʻokele ʻana o BLG ke hoʻohuli nui i kēia mau loli i hoʻopili ʻia e DSS. ʻO ka mea aʻe, ua hoʻohana mākou iā ELISA e hoʻoholo i nā pae o nā cytokines mumū TNF-α, IL-1β, a me IL-6 i loko o ka ʻiʻo colon. Ua hōʻike pū nā hopena ua piʻi nui nā pae colonic o TNF-α, IL-1β, a me IL-6 i nā ʻiole i mālama ʻia me DSS, ʻoiai ua hōʻoluʻolu ka mālama ʻana o BLG i kēia mau piʻi (Kiʻi 2B).
Kiʻi 2 Hoʻopaʻa ʻo BLG i ka hōʻike ʻana o nā gene a me ka hana ʻana o nā cytokines proinflammatory TNF-α, IL-1β a me IL-6 i loko o ka colon o nā ʻiole i mālama ʻia me DSS.(A) Hōʻike ʻana o ka gene colonic o TNF-α, IL-1β a me IL-6; (B) nā pae protein colonic o TNF-α, IL-1β a me IL-6. Hōʻike ʻia nā ʻikepili ma ke ʻano he awelika ± SEM (n = 4–6).#p < 0.05 a i ʻole ##p < 0.01 a i ʻole ###p < 0.001 vs ka hui kaohi (Con); *p < 0.05 a i ʻole **p < 0.01 vs hui DSS.
He mea koʻikoʻi ka dysbiosis ʻōpū i ka pathogenesis o UC.24 No ka noiʻi ʻana inā hoʻololi ʻo BLG i ka microbiota ʻōpū o nā ʻiole i mālama ʻia me DSS, ua hana ʻia ka hoʻonohonoho ʻana o 16S rRNA e kālailai i ke kaiāulu bacteria o nā mea o loko o ka ʻōpū. Hōʻike ka kiʻikuhi Venn e kaʻana like nā hui ʻekolu i 385 OTUs. I ka manawa like, loaʻa i kēlā me kēia hui nā OTU kū hoʻokahi (Kiʻi 3A). Eia kekahi, ua hōʻike ka helu kuhikuhi Chao1 a me ka helu kuhikuhi Shannon i hōʻike ʻia ma ke Kiʻi 3B a me C ua hoʻemi ʻia ke ʻano like ʻole o ke kaiāulu o ka microbiota ʻōpū i nā ʻiole i mālama ʻia me BLG, ʻoiai ua emi nui ka helu kuhikuhi Shannon i ka hui i mālama ʻia me BLG. Ua hoʻohana ʻia ka loiloi ʻāpana nui (PCA) a me ka loiloi hoʻonohonoho nui (PCoA) e hoʻoholo i nā ʻano clustering ma waena o nā hui ʻekolu a hōʻike i ka hoʻokaʻawale maopopo ʻana o ke ʻano kaiāulu o nā ʻiole i mālama ʻia me DSS ma hope o ka mālama ʻana me BLG (Kiʻi 3D a me E). Hōʻike kēia mau ʻikepili ua hoʻopilikia nui ka mālama ʻana me BLG i ke ʻano kaiāulu o nā ʻiole me ka colitis i hoʻokomo ʻia e DSS.
Kiʻi 3 Hoʻololi ʻo BLG i ke ʻano like ʻole o ka microbiota ʻōpū i loko o nā ʻiole me ka colitis i hoʻokomo ʻia e DSS. (A) Kiʻikuhi Venn o OTU, (B) Kuhikuhi Chao1, (C) Kuhikuhi waiwai o Shannon, (D) Kuhikuhi helu Principal Component Analysis (PCA) o OTU, (E) Kuhikuhi OTU Principal Coordinate Analysis (PCoA) Kiʻi. Hōʻike ʻia nā ʻikepili ma ke ʻano he awelika ± SEM (n = 6).**p < 0.01 vs hui DSS.
No ka loiloi ʻana i nā loli kikoʻī i loko o ka microbiota fecal, ua kālailai mākou i ka haku mele ʻana o ka microbiota ʻōpū ma nā pae taxonomic āpau. E like me ka mea i hōʻike ʻia ma ke Kiʻi 4A, ʻo ka phyla nui i nā hui āpau ʻo Firmicutes lāua ʻo Bacteroidetes, a ukali ʻia e Verrucomicrobia. Ua hoʻonui nui ʻia ka nui o nā lakio Firmicutes a me Firmicutes/Bacteroidetes i nā kaiāulu microbial fecal o nā ʻiole i mālama ʻia e DSS i hoʻohālikelike ʻia me nā ʻiole kaohi, a ua hoʻohuli nui ʻia kēia mau loli ma hope o ka mālama ʻana iā BLG. Ma ke ʻano kūikawā, ua hoʻonui nui ka mālama ʻana iā BLG i ka nui o Verrucobacterium i loko o nā feces o nā ʻiole me ka colitis i hoʻokomo ʻia e DSS. Ma ka pae ʻohana, ua noho ʻia nā kaiāulu microbial fecal e Lachnospiriaceae, Muribaculaceae, Akkermansiaceae, Ruminococcaceae a me Prevotellaceae (Kiʻi 4B). I ka hoʻohālikelike ʻia me ka hui DSS, ua hoʻonui ka emi ʻana o BLG i ka nui o Akkermansiaceae, akā ua hoʻemi i ka nui o Lachnospiraceae a me Ruminococcaceae. ʻIke ʻia, ma ka genus pae, ua noho ʻia ka microbiota fecal e Lachnospira_NK4A136_group, Akkermansia lāua ʻo Prevotellaceae_UCG-001 (Kiʻi 4C). Ua hōʻike pū kēia ʻike ua hoʻohuli maikaʻi ka mālama ʻana o BLG i ka hemahema o ka microbiota i ka pane ʻana i ka pilikia DSS, i hōʻailona ʻia e ka emi ʻana o Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas lāua ʻo Oscillibacter, a me ka piʻi ʻana o Akkermansia lāua ʻo Prevotellaceae_UCG-001.
Kiʻi 4 Hoʻololi ʻo BLG i ka nui o ka microbiota ʻōpū i nā ʻiole colitis i hoʻokomo ʻia e DSS. (A) Ka nui o ka microbiota ʻōpū ma ka pae phylum; (B) Ka nui o ka microbiota ʻōpū ma ka pae ʻohana; (C) Ka nui o ka microbiota ʻōpū ma ka pae genus. Hōʻike ʻia nā ʻikepili ma ke ʻano he awelika ± SEM (n = 6).#p < 0.05 a i ʻole ###p < 0.001 vs ka hui kaohi (Con); *p < 0.05 a i ʻole **p < 0.01 a i ʻole ***p < 0.001 vs hui DSS.
Ke noʻonoʻo nei ʻo nā waikawa momona kaulahao pōkole (SCFAs) nā metabolites nui o Akkermansia lāua ʻo Prevotellaceae_UCG-001, ʻoiai ʻo ka acetate, propionate a me ka butyrate nā SCFA nui loa i ka lumen ʻōpū, 25-27 ke hana nei mākou i kā mākou noiʻi. E like me ka mea i hōʻike ʻia ma ke Kiʻi 5, ua hoʻemi nui ʻia ka fecal acetate, propionate, a me ka butyrate concentrations i ka hui i mālama ʻia me DSS, ʻoiai hiki i ka mālama ʻana o BLG ke kāohi nui i kēia hōʻemi.
Kiʻi 5. Hoʻonui ʻo BLG i nā pae o SCFAs i loko o nā feces o nā ʻiole me ka colitis i hoʻokomo ʻia e DSS. (A) ʻO ka nui o ka waikawa acetic i loko o nā feces; (B) ka nui o ka waikawa propionic i loko o nā feces; (C) ka nui o ka waikawa butyric i loko o nā feces. Hōʻike ʻia nā ʻikepili ma ke ʻano he awelika ± SEM (n = 6). #p < 0.05 a i ʻole ##p < 0.01 vs ka hui kaohi (Con); *p < 0.05 a i ʻole **p < 0.01 vs hui DSS.
Ua helu hou mākou i ka coefficient correlation Pearson ma waena o ka genus-level differential SCFA a me ka fecal microbiota. E like me ka mea i hōʻike ʻia ma ke Kiʻi 6, ua pili pono ʻo Akkermansia me ka hana ʻana o ka propionic acid (Pearson = 0.4866) a me ka butyric acid (Pearson = 0.6192). I ka hoʻohālikelike ʻana, ua pili maikaʻi ʻole ʻo Enteromonas lāua ʻo Oscillobacter me ka hana acetate, me nā coefficients Pearson o 0.4709 a me 0.5104, kēlā me kēia. Pēlā nō, ua pili maikaʻi ʻole ʻo Ruminococcaceae_UCG-014 me ka hana ʻana o ka propionic acid (Pearson = 0.4508) a me ka butyric acid (Pearson = 0.5842), kēlā me kēia.
Kiʻi 6 Ka loiloi pilina Pearson ma waena o nā SCFA like ʻole a me nā microbes colonic. (A) Enteromonas me ka waikawa acetic; (B) Concussion bacillus me ka waikawa acetic; (C) Akkermansia vs propionic acid; (D) Ruminococcus_UCG-014 me ka waikawa propionic; (E) Akkermansia me ka waikawa butyric; (F) ) Ruminococcus _UCG-014 me ka waikawa butyric.
ʻO ka Glucagon-like peptide-1 (GLP-1) kahi huahana post-translational kikoʻī o ka proglucagon (Gcg) me nā waiwai anti-inflammatory.28 E like me ka mea i hōʻike ʻia ma ke Kiʻi 7, ua hoʻoulu ʻo DSS i ka emi nui ʻana o ka hōʻike ʻana o ka Gcg mRNA. Hiki i ka mālama ʻana o Colon a me BLG ke hoʻohuli nui i ka hōʻemi ʻana o Gcg i hoʻokomo ʻia e DSS i hoʻohālikelike ʻia me ka hui kaohi (Kiʻi 7A). I ​​ka manawa like, ua emi nui ka pae o GLP-1 i loko o ke serum i ka hui i mālama ʻia e DSS, a hiki i ka mālama ʻana o BLG ke pale nui i kēia hōʻemi (Kiʻi 7B). ʻOiai hiki i nā waikawa momona kaulahao pōkole ke hoʻoulu i ka hoʻokuʻu ʻana o GLP-1 ma o ka hoʻāla ʻana o G-protein-coupled receptor 43 (GRP43) a me G-protein-coupled receptor 41 (GRP41), ua nānā pū mākou iā GPR41 a me GRP43 i loko o ka colon o nā ʻiole colitis a ua ʻike ʻia ua emi nui ka hōʻike ʻana o ka colonic mRNA o GRP43 a me GPR41 ma hope o ka hoʻokūkū DSS, a hiki i ka mālama ʻana o BLG ke hoʻopakele pono i kēia mau emi ʻana (Kiʻi 7C a me D).
Kiʻi 7 Hoʻonui ʻo BLG i nā pae serum GLP-1 a me ka colonic Gcg, GPR41 a me ka hōʻike ʻana o ka GRP43 mRNA i nā ʻiole i mālama ʻia me DSS.(A) Hōʻike ʻana o ka Gcg mRNA i loko o ka ʻiʻo colon; (B) Pae GLP-1 i loko o ka serum; (C) Hōʻike ʻana o ka GPR41 mRNA i loko o ka ʻiʻo colon; (D) Hōʻike ʻana o ka GPR43 mRNA i loko o ka ʻiʻo colon. Hōʻike ʻia nā ʻikepili ma ke ʻano he awelika ± SEM (n = 5–6).#p < 0.05 a i ʻole ##p < 0.01 vs ka hui kaohi (Con); *p < 0.05 vs hui DSS.
ʻOiai hiki i ka mālama ʻana o BLG ke hoʻonui i nā pae serum GLP-1, ka hōʻike ʻana o ka colonic Gcg mRNA, a me nā pae fecal SCFA i nā ʻiole i mālama ʻia me DSS, ua nānā hou mākou i ka acetate, propionate, a me butyrate a me nā ʻiole kaohi (F-Con), DSS colitis (F-Con) -DSS) a me nā ʻiole colitis i mālama ʻia me BLG (F-BLG) ma ka hoʻokuʻu ʻana o GLP-1 mai nā cell epithelial colonic murine mua. E like me ka mea i hōʻike ʻia ma ke Kiʻi 8A, nā cell epithelial colonic mouse mua i mālama ʻia me 2 mM acetic acid, propionic acid, a me ka butyric acid, kēlā me kēia, ua hoʻoulu nui i ka hoʻokuʻu ʻana o GLP-1, e kūlike me nā haʻawina mua.29,30 Pēlā nō, ʻo nā F-Con, F-DSS, a me F-BLG āpau (like me 0.25 g o nā feces) i hoʻoulu nui i ka hoʻokuʻu ʻana o GLP-1 mai nā cell epithelial colonic murine mua. ʻO ka mea nui, ʻo ka nui o GLP-1 i hoʻokuʻu ʻia e nā cell epithelial colonic mouse mua i mālama ʻia me F-DSS ua haʻahaʻa loa ia ma mua o F-Con a me F-BLG mua i mālama ʻia. nā pūnaewele epithelial colonic ʻiole. (Kiʻi 8B). Hōʻike kēia mau ʻikepili ua hoʻihoʻi nui ka mālama ʻana o BLG i ka hana ʻana o GLP-1 i loaʻa mai ka SCFA.
Kiʻi 8 Hoʻoulu ka SCFA i loaʻa mai BLG i ka hoʻokuʻu ʻana o GLP-1 mai nā pūnaewele epithelial colonic murine mua. (A) Hoʻoulu ka waikawa acetic, ka waikawa propionic, a me ka waikawa butyric i ka hoʻokuʻu ʻana o GLP-1 mai nā pūnaewele epithelial colonic murine mua; (B) nā ʻāpana fecal i hoʻoulu ʻia e F-Con, F-DSS a me F-BLG nā pūnaewele epithelial colonic murine mua Ka nui o GLP-1 i hoʻokuʻu ʻia. Ua kau ʻia nā Aliquots o nā pūnaewele epithelial colonic i loko o nā kīʻaha petri lalo aniani a mālama ʻia me 2 mM acetic acid, propionic acid, butyric acid, a me nā ʻāpana fecal F-Con, F-DSS, a me F-BLG (like me 0.25 g feces), kēlā me kēia. 2 hola ma 37°C, 5% CO2, kēlā me kēia. Ua ʻike ʻia ka nui o GLP-1 i hoʻokuʻu ʻia mai nā pūnaewele epithelial colonic murine mua e ELISA. Hōʻike ʻia nā ʻikepili ma ke ʻano he awelika ± SEM (n = 3).#p < 0.05 a i ʻole ##p < 0.01 vs. blank a i ʻole F-Con; *p < 0.05 e kū'ē iā F-DSS.
Nā pōkole: Ace, waikawa acetic; Pro, waikawa propionic; eia naʻe, waikawa butyric; F-Con, ʻāpana fecal mai nā ʻiole kaohi; F-DSS, ʻāpana fecal mai nā ʻiole colitis; F-BLG, mai ka colon i mālama ʻia e BLG Nā ʻāpana fecal o nā ʻiole mumū.
Ua helu ʻia e ka World Health Organization ma ke ʻano he maʻi paʻakikī, ke lilo nei ka UC i mea weliweli honua; akā naʻe, ua kaupalena ʻia nā ʻano hana kūpono no ka wānana ʻana, ka pale ʻana, a me ka mālama ʻana i ka maʻi. No laila, aia kahi pono wikiwiki e ʻimi a hoʻomohala i nā hoʻolālā therapeutic palekana a maikaʻi hoʻi no UC. ʻO nā hoʻomākaukau lāʻau lapaʻau Kina kuʻuna he koho hoʻohiki no ka mea ua hōʻike ʻia nā hoʻomākaukau lāʻau lapaʻau Kina kuʻuna he nui i ka mālama ʻana i ka UC i ka heluna kanaka Kina i nā kenekulia, a he mau mea olaola olaola a me nā mea kūlohelohe lākou a pau i ʻole e pōʻino i nā kānaka a me nā holoholona.31,32 Ua manaʻo kēia haʻawina e ʻimi i kahi hoʻomākaukau lāʻau lapaʻau Kina kuʻuna palekana a maikaʻi no ka mālama ʻana i ka UC a e ʻimi i kāna ʻano hana. ʻO BLG kahi ʻano lāʻau lapaʻau Kina kaulana i hoʻohana ʻia e mālama i ka maʻi flu.8,33 Ua hōʻike ka hana ma kā mākou keʻena hoʻokolohua a me nā mea ʻē aʻe ʻo indigo, kahi huahana lāʻau lapaʻau Kina kuʻuna i hana ʻia mai ka mea maka like me BLG, hōʻike i ka pono koʻikoʻi i ka mālama ʻana i ka UC i nā kānaka a me nā holoholona.4,34 Eia naʻe, ʻaʻole maopopo nā hopena anti-colitis o BLG a me kona hopena. ʻAʻole maopopo ke ʻano hana.Ma ke aʻo ʻana i kēia manawa, hōʻike kā mākou mau hopena e hoʻēmi pono ana ʻo BLG i ka mumū colonic i hoʻokomo ʻia e DSS, kahi e pili ana me ka modulation o ka microbiota gut a me ka hoʻihoʻi ʻana o ka hana ʻana o GLP-1 i loaʻa mai ka ʻōpū.
Ua ʻike maopopo ʻia ua hōʻike ʻia ka UC e nā wā relapsing me nā hiʻohiʻona lapaʻau maʻamau, e like me ka pohō kaumaha, ka maʻi diarrhea, ke kahe ʻana o ke koko rectal, a me ka hōʻino nui ʻana o ka mucosal colonic.35 No laila, ua lawelawe ʻia ka colitis relapsing mau ma ka lawelawe ʻana i ʻekolu mau pōʻaiapuni o 1.8% DSS no ʻelima mau lā, a ukali ʻia e ʻehiku mau lā o ka wai inu. E like me ka mea i hōʻike ʻia ma ke Kiʻi 1B, ua hōʻike ka pohō kaumaha a me nā helu DAI i ka hoʻokomo pono ʻana o ka colitis relapsing mau. Ua hōʻike nā ʻiole i ka hui i mālama ʻia me BLG i ka hoʻōla upshift mai ka lā 8, kahi ʻokoʻa loa mai ka lā 24. Ua ʻike ʻia nā loli like ma ka helu DAI, e hōʻike ana i ka hoʻomaikaʻi ʻana i ka hoʻomaikaʻi lapaʻau o ka colitis. Ma ke ʻano o ka hōʻeha ʻana o ka colon a me ke kūlana mumū, ʻo ka lōʻihi o ka colon, ka hōʻino ʻana o nā ʻiʻo colon, a me ka hōʻike ʻana o ka gene a me ka hana ʻana o nā cytokines proinflammatory TNF-α, IL-1β, a me IL-6 i loko o nā ʻiʻo colon ua hoʻomaikaʻi nui ʻia ma hope o ka mālama ʻana o BLG. Ma ke ʻano hui, hōʻike maopopo kēia mau hopena he pono ka BLG i ka mālama ʻana i ka colitis relapsing mau i nā ʻiole.
Pehea e hoʻokō ai ʻo BLG i kāna mau hopena pharmacological? Ua hōʻike ʻia nā haʻawina mua he nui e pāʻani ana ka microbiota gut i kahi kuleana koʻikoʻi i ka pathogenesis o UC, a ua puka mai nā ʻano hana i hoʻokumu ʻia i ka microbiome a me ka microbiome-targeted ma ke ʻano he hoʻolālā hoihoi loa no ka mālama ʻana i ka UC. Ma ke aʻo ʻana i kēia manawa, ua hōʻike mākou ua hopena ka mālama ʻana o BLG i nā loli koʻikoʻi i ka haku mele ʻana o ka microbiota gut, e hōʻike ana e pili ana ka hopena pale o BLG e kūʻē i ka colitis i hoʻokomo ʻia e DSS i ka modulation o ka microbiota gut. Kūlike kēia ʻike me ka manaʻo e hoʻolālā hou ana i ka homeostasis o ka microbiota gut he ala koʻikoʻi ia e hoʻomaopopo ai i ka pono o nā hoʻomākaukau TCM.36,37 ʻO ka mea nui, ʻo Akkermansia kahi bacteria Gram-negative a anaerobic strictly e noho ana i loko o ka papa mucus o ka ʻōpū, kahi e hoʻohaʻahaʻa ai i nā mucins, hana i ka propionic acid, hoʻoulu i ka hoʻokaʻawale ʻana o nā cell goblet, a mālama i ka mucosa. hana o ka pale mucosa.26 Hōʻike nā ʻikepili lapaʻau a me nā holoholona he nui e pili nui ana ʻo Akkermansia me ka mucosa olakino,38 a me ka lawelawe waha o Akkermansia spp. hiki ke hoʻomaikaʻi nui i ka mumū mucosal.39 Hōʻike kā mākou ʻikepili o kēia manawa ua hoʻonui nui ʻia ka nui o Akkermansia ma hope o ka mālama ʻana iā BLG. Eia kekahi, ʻo Prevotellaceae_UCG-001 kahi bacteria hana SCFA.27 Ua hōʻike ʻia nā haʻawina he nui ua loaʻa ʻo Prevotellaceae_UCG-001 i ka nui haʻahaʻa i loko o nā feces o nā holoholona me ka colitis.40,41 Hōʻike pū kā mākou ʻikepili o kēia manawa hiki i ka mālama ʻana iā BLG ke hoʻonui nui i ka nui o Prevotellaceae_UCG-001 i loko o ka colon o nā ʻiole i mālama ʻia e DSS. I ka hoʻohālikelike ʻana, ʻo Oscillibacter kahi bacteria mesophilic, strictly anaerobic.42 ua hōʻike ʻia ua hoʻonui nui ʻia ka nui o Oscillibacter i nā ʻiole UC a ua pili pono me nā pae IL-6 a me IL-1β a me nā helu pathological.43,44 ʻO ka mea nui, ua hoʻemi nui ka mālama ʻana iā BLG i ka nui o Oscillibacter i loko o nā feces o nā ʻiole i mālama ʻia e DSS. ʻO ka mea nui, ʻo kēia mau bacteria i hoʻololi ʻia e BLG nā bacteria hana SCFA nui loa. Nui nā mea ma mua Ua hōʻike ʻia nā haʻawina i nā hopena maikaʻi o nā SCFA ma ka mumū o ka colonic a me ka pale ʻana i ka pono o ka epithelial intestinal.45,46 Ua ʻike pū kā mākou ʻikepili i kēia manawa ua hoʻonui nui ʻia nā ʻano o ka SCFA acetate, propionate, a me ka butyrate i loko o nā feces i mālama ʻia e DSS i nā ʻiole i mālama ʻia e BLG. I ka hui pū ʻia ʻana, hōʻike maopopo kēia mau ʻike e hiki i ka mālama ʻana o BLG ke hoʻoikaika maikaʻi i ka bacteria hana SCFA i hoʻokomo ʻia e DSS i nā ʻiole me ka colitis relapsing mau.
ʻO GLP-1 kahi incretin i hana nui ʻia ma ka ileum a me ka colon a he kuleana koʻikoʻi kāna i ka hoʻopaneʻe ʻana i ka ʻōpū a me ka hoʻohaʻahaʻa ʻana i ke kō koko postprandial.47 Hōʻike nā hōʻike e hiki i ka dipeptidyl peptidase (DPP)-4, kahi agonist receptor GLP-1, a me kahi nanomedicine GLP-1 ke hōʻoluʻolu maikaʻi i ka mumū o ka ʻōpū i nā ʻiole.48-51 E like me ka hōʻike ʻana ma nā haʻawina mua, ua pili nā kiʻekiʻe o ka SCFA me nā pae plasma GLP-1 i loko o nā kānaka a me nā ʻiole.52 Hōʻike kā mākou ʻikepili o kēia manawa ma hope o ka mālama ʻana iā BLG, ua hoʻonui nui ʻia nā pae serum GLP-1 a me ka hōʻike ʻana o Gcg mRNA. Pēlā nō, ua hoʻonui nui ʻia ka hoʻokuʻu ʻana o GLP-1 i nā moʻomeheu colonic ma hope o ka hoʻoulu ʻana me nā ʻāpana fecal mai nā ʻiole colitis i mālama ʻia e BLG i hoʻohālikelike ʻia me ka hoʻoulu ʻana me nā ʻāpana fecal mai nā ʻiole colitis i mālama ʻia e DSS. Pehea e hoʻopilikia ai nā SCFA i ka hoʻokuʻu ʻana o GLP-1?Gwen Tolhurst et al. ua hōʻike ʻia e hiki i ka SCFA ke hoʻoulu i ka hoʻokuʻu ʻana o GLP-1 ma o GRP43 a me GPR41.29 Hōʻike pū kā mākou ʻikepili i kēia manawa e hoʻonui nui ka mālama ʻana o BLG i ka hōʻike mRNA o GRP43 a me GPR41 i loko o ka colon o nā ʻiole i mālama ʻia me DSS. Hōʻike kēia mau ʻikepili e hiki i ka mālama ʻana o BLG ke hoʻihoʻi i ka hana GLP-1 i hoʻolaha ʻia e SCFA ma ka hoʻoulu ʻana iā GRP43 a me GPR41.
He lāʻau lapaʻau lōʻihi ʻo BLG ma Kina. ʻO ka nui o ka BLG i ʻae ʻia i nā ʻiole Kunming he 80g/Kg, a ʻaʻohe ʻona ʻino i ʻike ʻia.53 I kēia manawa, ʻo ka nui i ʻōlelo ʻia no BLG (me ke kō ʻole) i loko o ke kanaka he 9-15 g/lā (3 manawa i ka lā). Ua hōʻike kā mākou noiʻi ua hoʻomaikaʻi ʻo BLG ma 1g/Kg i ka colitis relapsing mau i hoʻoulu ʻia e DSS i nā ʻiole. Ua kokoke kēia nui i ka nui o BLG i hoʻohana ʻia ma ke ʻano lapaʻau. Ua ʻike pū kā mākou noiʻi ua hoʻopili ʻia kāna ʻano hana, ma ka liʻiliʻi ma kahi hapa, e nā hoʻololi ʻana i ka microbiota ʻōpū, ʻo ia hoʻi nā bacteria hana SCFA, e like me Akkermansia lāua ʻo Prevotellaceae_UCG-001, e hoʻihoʻi i ka hana ʻana o GLP-1 i loaʻa mai ka ʻōpū. Hōʻike kēia mau ʻike e pono ke noʻonoʻo hou ʻia ʻo BLG ma ke ʻano he mea lapaʻau kūpono no ka mālama ʻana i ka colitis lapaʻau. Eia nō naʻe, ʻo ke ʻano kikoʻī e hoʻololi ai i ka microbiota ʻōpū e pono e hōʻoia ʻia e nā ʻiole nele i ka microbiota a me ka hoʻoili ʻana o ka bacteria fecal.
ʻAce, waikawa acetic; akā, waikawa butyric; BLG, pandan; DSS, dextran sodium sulfate; DAI, papa kuhikuhi hana maʻi; DPP, dipeptidyl peptidase; FID, mea ʻike ionization lapalapa; F-Con, kaohi i nā ʻāpana fecal o nā ʻiole; F-DSS, nā ʻāpana fecal o nā ʻiole colitis DSS; F-BLG, nā ʻāpana fecal o nā ʻiole colitis i mālama ʻia e BLG; GLP-1, glucagon-like peptide-1; Gcg, glucagon; gas chromatography, gas chromatography; GRP43, G protein-coupled receptor 43; GRP41, G protein-coupled receptor 41; H&E, hematoxylin-eosin; HBSS, Hanks' Balanced Salt Solution; OTC, OTC; PCA, loiloi ʻāpana nui; PCoA, loiloi hoʻonohonoho nui; Pro, propionic acid; SASP, sulfasalazine; SCFA, nā waikawa momona kaulahao pōkole; lāʻau lapaʻau Kina, lāʻau lapaʻau kuʻuna Kina; UC, ulcerative colitis.
Ua ʻāpono ʻia nā kaʻina hana hoʻokolohua āpau e ke Kōmike Hoʻopono Holoholona o ke Kulanui ʻo Peking Shenzhen-Hong Kong University of Science and Technology Medical Center (Shenzhen, Kina) e like me nā Alakaʻi ʻAhahui a me nā Hoʻoponopono Holoholona (helu hoʻopono A2020157).
Ua hāʻawi nui nā mea kākau a pau i ka manaʻo a me ka hoʻolālā, ka loaʻa ʻana o ka ʻikepili, a i ʻole ka nānā ʻana a me ka wehewehe ʻana i ka ʻikepili; ua komo i ke kākau ʻana i ka ʻatikala a i ʻole ka hoʻoponopono hou ʻana i nā ʻike noʻonoʻo koʻikoʻi; ua ʻae e waiho i ka palapala i ka puke pai o kēia manawa; ua ʻae hope ʻia ka mana no ka paʻi ʻana; Kuleana no nā ʻano āpau o ka hana.
Ua kākoʻo ʻia kēia hana e ka National Natural Science Foundation of China (81560676 a me 81660479), ka papahana papa mua o ke Kulanui ʻo Shenzhen (86000000210), ka Shenzhen Science and Technology Innovation Committee Fund (JCYJ20210324093810026), a me ka Guangdong Provincial Medical Science and Technology Research Fund (A2020157 a me A2020272), Guizhou Medical University Pharmacy Guizhou Province Funded by Key Laboratory (YWZJ2020-01) a me Peking University Shenzhen Hospital (JCYJ2018009).
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