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Ban-Lan-Gen granules dwoko piny dextran sodium sulfate-induced chronic relapsing colitis i kom oyot kun loko gut microbiota ki dwoko intestinal SCFA Derived-GLP-1 production
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 Haitao21Peking University Shenzhen Hospital Department of Pharmacy, Shenzhen, Republics of China; 2Shenzhen University Health Science Center School of Pharmacy, Shenzhen, People's Republic of China; 3Guizhou Medical University Engineering Technology Center Research of Ethnic Medicine and Traditional Chinese Medicine Development and Application Ministry of Education, Guizhou Provincial Key Laboratory of Pharmacy, Guizhou Medical University , Guiyang, People's Republic of China; 4 Dul ma kwano lok ma mako ic, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China; 5 Gang kwan me yat, Guizhou Medical University, State Key Laboratory me tic pa yadi ma ki tiyo kwede ki tic kwede, Guiyang; 6 Dul ma kwano lok kom yot kom, Peking University Shenzhen Hospital, Shenzhen, China [email protected] Shen Xiangchun, Gang kwan me Pharmacy, Guizhou Medical University, Guizhou, People's Republic of China, 550004, Email [email protected] Gin ma mite: GLP-1-based therapy obedo yoo manyen me cango two ma mako ic. (BLG) granules obedo gin ma ki ngeyo ma gengo kwidi TCM ma nyutu tic me gengo pong pa kom i cango two ma pat pat. Ento, tic ne me gengo pong pa kom i kom two ma mako ic ki kit ma en tiyo kwede pwod pe nen maber.YO ME TIMO: Me keto dextran sodium sulfate (DSS)-induced chronic colpsing activity i kom two ma mako ic. lanyut, lanyut me awano, ki rwom me cytokine ma kelo two ki tiimo me neno kit ma BLG gwoko kwede. Adwogi pa BLG i kom jami makwo ma i ic ki ic ​​onongo ki nyutu ki rwom me GLP-1 i remo ki colonic Gcg, GPR41, ki GRP43 ma ki nyutu, rwom me microbiota i ic, rwom me GLP SC ma ki kwanyo ki i ic, ki GLP-1 colonic epithelial cells SCFA-derived GLP-1 production.Adwogi: Yat me BLG odwoko piny pek pa kom, DAI, colon shortening, colon tissue damage, ki proinflammatory cytokine levels me TNF-α, IL-1β, ki IL-6 i colon tissue. Medo i kom meno, yat BLG twero dwoko GPRG4 GLP-1 piny. ki GRP43 ma ki nyutu ki rwom me GLP-1 i remo i kom ler ma ki lwongo ni colitis mice, ki medo SCFA-producing bacteria ma calo Akkermansia ki Prevotellaceae_UCG-001, ki dwoko piny wel bacteria ma calo Eubacterium_xylanophilum_group, Ruminococcaceae_Gmonantes104, Imonantes ki Icbacbaliter. Medo ikom meno, yat BLG twero medo rwom pa SCFAs i ic pa oyot ma tye ki two colitis. I kare acel, temo ma kitimo i kom ler bene onyutu ni gin ma ki kwanyo ki i kom oyot ma ki miyo iye BLG twero weko ler ma ki lwongo ni Murine colonic epithelial cells ma ki lwongo ni GLP-1. Lacen: Gin ma kinongo ni nyutu ni BLG tye ki adwogi i kom two ma mako ic. BLG tye ki kero me bedo calo yoo me cang, kadi bed ni ki loko jami ma kwo i ic ki dwoko SCFA-derived GLP-1 ma i ic. Yat ma twero konyo two ma mako ic. Lok ma pire tek: colitis, Ban-Lan-Gen granules, gut microbiota, short-chain fatty acids, GLP-1
Two ma ki lwongo ni Ulcerative colitis (UC) obedo two ma mako ic ki ic ​​ma rii pi kare malac ma nyutu calo cado ma bino kare ki kare, arem i ic, rwenyo pek pa kom, ki remo ma mol ki ic.1 I kare ni, wel two UC tye ka mede i lobo ma onongo two ne nok iye, medo ki China, ki kit me kwo pa Western tye ka mede. kelo peko madit bot yotkom pa lwak ki tye ki adwogi marac i kom kero pa lutwo me tic ki kwo maber. Ki lok adaa, kit ma two UC cako kwede pwod pe tye atir, ento dano mapol giye ni jami ma kwako kodi dano, jami ma orumowa, jami ma kwo i ic, ki kit ma kom dano gwoko kwede kom dano weng gi konyo i dongo pa UC.3 Kadi wa i kare ni, pe tye yat mo me cango two UC, ki kit me cango two ni tye ka cito i ot yat kelo ki gwoko cang, konyo cang pa remo, ki dwoko piny dwogo pa two. Yat macon tye iye aminosalicylates, corticosteroids, immunosuppressants, ki biologics. Ento, yadi magi pe twero kelo adwogi ma miite pi adwogi marac ma gi kelo.4 I kare ni, kwan mapol onyutu ni yadi macon me China (MTC) tye ki adwogi maber twero me konyo me juku UC ki peko manok, ma nyutu ni yubu yoo me cang TCM manyen obedo yoo me cang maber pi UC.5-7��
Banlangen Granules (BLG) obedo yat me tekwaro pa jo China ma ki yubu ki i pii ma ki kwanyo ki i yat Banlangen.8 Medo i kom tic ne me gengo two, BLG nyutu tic me gengo two ma mako two ma pat pat.9,10 Medo ikom meno, glucosinolates (R,S-goitrin, progoitrin, ki glucobin ki isolated ma ki nongo ki i pii ma ki kwanyo ki i Radix isatidis) ki nucleosides (hypoxanthine, adenosine, uridine ki guanosine) ki indigo alkaloids calo indigo ki indirubin.11,12 Kwan macon onyutu maber ni jami ma ki lwongo ni adenosine, uridine ki indirubin nyutu teko me lweny i kom two colitis i kom ler ma pat pat. Ento, pe tye kwan mo ma kitimo ma nyutu ni BLG tiyo maber i kom two colitis. I kwan man, wa kwedo kit ma BLG gwoko kwede dextran sodium sulfate (DSS)-induced chronic relapsing colitis i C57BL/6 mice ki wanongo ni tic ki BLG ki dog okelo DSS-induced chronic relapsing colips Pong pa remo, kit ma en doro kwede jami ma kwo i ic ki dwoko rwom me glucagon-ma calo peptide-1 (GLP-1) ma aa ki i ic.
BLG granules (ma pe ki cukal, NMPA-approved Z11020357; Beijing Tongrentang Technology Development Co., Ltd., Beijing, China; namba me dul: 20110966) ki wilo ki i ot yat. DSS (Molecular Weight: 36,000–500,000) ki wilo ki i ton MP Biologicals (Santa Ana, USA). Sulfasalazine (SASP) (≥ 98% maleng), hematoxylin ki eosin ki wilo ki bot Sigma-Aldrich (St. Louis, MO, USA). Mouse TNF-α, IL-1β ki IL-6 luminex Elisa assay kits ki wilo ki bot R&D systemassitic (Mine, MNacetic, USA). propionic acid, ki butyric acid ki wilo ki bot Aladdin Industries (Shanghai, China).2-Ethylbutyric acid ki wilo ki bot Merck KGaA (Darmstadt, Germany).
6-8-week-old male C57BL/6 mice (body weight 18-22 g) ki wilo ki bot Beijing Wetahe Laboratory Animal Technology Co., Ltd. (Beijing, China) ki ki gwoko gi i kabedo ma tye ki 22 ± 2 °C ki 12 h light/ dark cycle ki miyo gi cam ma rwate ki pii ma ki mato ki rodent acel. cabit me rwate ki kabedo manyen. Ki poko oyot ni i dul angwen: dul ma ki temo, dul ma ki lwongo ni DSS model, dul ma ki miyo SASP (200 mg/kg, oral) ki dul ma ki miyo BLG (1 g/kg, oral). Kit ma ki nyutu kwede i cal 1A, malube ki kwan wa mukato, two ma mako ic ma bino pi kare malac onongo ki kelo i oyo i 3% pa ​​DSS pi 18%. Nino 5, ki lubo ki pii ma ki yubu pi nino 7, malube ki kwan wa mukato ni.18 Twoni ma ki miyo SASP ki BLG ki miyo SASP ki BLG, kit meno, nino weng cake i nino 0. Malube ki temo macon, ki keto rwom me BLG i 1 g/kg. I kare meno, rwom me SASP ki keto i 20/kg lok ma ki coyo.4 Dul ma ki temo ki ma ki lwongo ni DSS gunongo pii marom i kare me temo ni.
cal 1 BLG konyo DSS-induced chronic relapsing colitis i kom oyoo. (A) kit ma ki yubu kwede two ma mako ic ki kit me cango ne, (B) alokaloka me pek pa kom, (C) rwom me tic pa two (DAI), (D) bor pa ic, (E) cal ma nyutu ic, (F) H&E ma ki keto i ic (G wel. Lok ma ki nongo ki nyutu calo rwom me ± SEM (n = 6).##p < 0.01 onyo ###p < 0.001 ki dul ma ki temo (Con); *p < 0.05 onyo **p < 0.01 onyo ***p < 0.001 ki dul pa DSS.
Pek pa kom, rwom me ic, ki remo ma aa ki i ic ki coyo piny nino ducu. Ki nongo kit ma two tiyo kwede (DAI) ki keto wel pek pa kom, rwom me ic, ki remo ma aa ki i ic kit ma kiloko kwede con.19 I agiki me temo, ki neko oyot weng ki remo, ic ki ic ​​ki kwanyo pi temo mukene.
Del kom ma ki lwongo ni colon tissue ni ki keto i formalin ki ki keto i paraffin. 5-micron dul ma ki yubu ki ki keto rangi i kome ki hematoxylin-eosin (H&E), ki dong ki keto wange ki ki keto i rwom ma calo ma kiloko iye con.
RNA weny ma ki kwanyo ki i kom ic ki kwanyo ki Trizol reagent (Invitrogen, Carlsbad, CA), ki lubo ki kwanyo cDNA ki reverse transcriptase (TaKaRa, Kusatsu, Shiga, Japan). Quantitative PCR kitimo kun kitiyo ki real-time PCR system ki SYBR Green Master (Roche, Basel, Switzerland, Switzerland genes ma ki coyo me doko β T). ngec ni ki kwano kun kitiyo ki yoo me 2-ΔΔCT. Gin ma ki lwongo ni gene primer sequences ki nyutu gi i Table 1.
Kwanyo cell me ic pa ler ma ki lwongo ni Primary mouse epithelial cell isolation ki culture ni kitimo kit ma onongo kiloko kwede con.20 Ki lok macek, colon pa ler ma mwaka gi tye 6-8 ki kwanyo woko inge neko gi ki cervical dislocation, ki dong ki yabo gi, ki miyo yat ma ki lwongo ni Hanks Balanced Salt Solution (HBSS, labongo calcium ki magneum) ki cut ma nok ki 50 mm. dul kom. I ngeye, ki juku dul kom ki 0.4 mg/mL collagenase XI (Sigma, Poole, UK) i DMEM ma pe ki culu ki ki centrifuge i 300 xg pi dakika 5 i rwom me lyeto me ot. Medo gin ni i DMEM (ki medo ki 10% fetal serum bovinenic, 10/10 units, ki peillin 100 μg/mL streptomycin) i 37 °C ki kato ki i nylon mesh (pore size ~250 μm). Ki keto dul kom ma ki lwongo ni colonic epithelial cells i gin ma ki lwongo ni glass-bottom dishes ki ki gwoko ki acetic acid, propionic acid, butyric acid, ki fouse extract pi cawa 37°C 5% CO2.
Gin ma ki lwongo ni colon tissue ni ki rwate ki PBS, ki rwom pa cytokines IL-6, TNF-α ki IL-1β i colon tissue ki nongo kun kitiyo ki luminex ELISA assay kits (R&D systems, Minneapolis, MN, USA). ELISA kit (Bioswamp, Wuhan, China) kit ma lucat wil owaco kwede.
DNA weny ki i ic ki kwanyo kun kitiyo ki jami ma kwanyo DNA (Tiangen, China). Kit ki dwong pa DNA ki pimo i ratio me 260 nm/280 nm ki 260 nm/230 nm, kit meno. I ngeye, kun kitiyo ki DNA acel acel ma ki kwanyo calo labol, ki kwanyo jami ma ki lwongo ni 338F (ACCCG) ki GAGCAGA86 (GGACTACHVGGGTWTCTAAT) ki otiiyo kwede me medo V3-V4 dul kom pa 16S rRNA gene i dul ma pat pat. Jami ma ki yubu ki PCR ki yubu kun kitiyo ki QIAquick Gel Extraction Kit (QIAGEN, Germany), ki kwano ki real-time PCR, ki ki keto i rwom ma opore kun kitiyo ki IlluminaMiseq PE300 sequencing platform (Fillumina, CA, USA). nyamo lok ma mako kwo pa dano, tic ki ngec ma ki nongo ki tiimo ma lubu cik ma ki coyo con.21,22 Ki lok macek, tic ki Cutadapt (V1.9.1) me kwanyo jami ma ki coyo ma pe ki ngeyo. OTUs ki keto gi kacel kun kitiyo ki UPARSE (version 7.0.1001) ki rwom me rwate pa 97%, ki UCHIME onongo kitiyo kwede me kwanyo jami ma ki lwongo ni chimer sequence classification ki community analysis. ki tiimo kun kitiyo ki RDP classifier (http://rdp.cme.msu.edu/) ma jenge i kom SILVA ribosomal RNA gene database.
Kit ma rwom me acid ma ki lwongo ni short-chain fatty acids (acetic acid, propionic acid, ki butyric acid) ki pimo kit ma ki waco kwede con ni Tao et al., ki alokaloka mogo.23 Ki lok manok, 100 mg me feces ki keto i 0.4 mL me pii ma ki kwanyo ion, ki lubo ki 0.1 mL me 0.1 mL me 0.5 mL me acid ki sulfuric 50 mL. 2-ethylbutyric acid (kit ma ki ngeyo kwede), ki dong ki yubu ki lyeto i 4°C. Centrifuge i 12,000 rpm pi dakika 15 i C. Gin ma odong ni ki kwanyo ki 0.5 mL me ether ki ki keto i GC me nyamo. Pi nyamo gas chromatography (GC), ki kwano jami ma ki nyutu kun kitiyo ki GC-2010 Plus gas chromatograph (Shimadzu, Inc) ma tye ki dector deteon. (FID). Poko ne kitimo kun kitiyo ki ZKAT-624 column, 30 m × 0.53 mm × 0.3 μm (Lanzhou Zhongke Antai Analytical Technology Co., Ltd., China). Ngec ni ki nongo ki tic ki GC solution software (Shimadzu, Inc.). Ratio me poko ne onwongo tye nitrogen: 10, ki nitrogen onwongo obedo yamo ma ki lwongo ni carrier, ki gin ma ki lwongo ni carrier onwongo obedo nitrogen, ki gas ma ki lwongo ni carrier onwongo tye nitrogen. kit ma mol kwede onwongo tye 6 mL/min. Kit ma ki keto kwede onwongo tye 1 μL. Lyeto pa gin ma ki keto iye ki gin ma nongo onwongo tye 300°C. Lyeto pa oven ni ki gwoko i 140°C pi dakika 13.5, ki dong ki medo 250°C i rwom me 120°C/min; lyeto ni ki gwoko pi dakika 5.
Ngec ni ki nyutu calo gin ma tye i kin ± bal ma ki ngeyo (SEM). Kit ma gin ma ki nongo ni pire tek kwede ki kwano ki one-way ANOVA ma lubu ki Duncan's multiple range test. GraphPad Prism 5.0 software (GraphPad Software Inc., San Diego, CA, USA) ki tiyo kwede pi kwano weny ki p < 0.05 ki ngeyo ni pire tek.
Ki ngeyo maber ni UC obedo two ma mako ic ma bino pi kare malac ki arem i ic, cado ki remo. Pi meno, DSS-induced chronic relapsing colitis i kom oyoo ki keto me pimo tic pa BLG me gengo two ic (Fig. 1A). Ka kiporo ki oyot ma ki kwanyo ki i dul ma ki kwanyo ki i DSS onongo pek pa kom gi odok piny. DAI, ki alokaloka eni odok cen i nge nino 24 me yat BLG (lanyut 1B ki C). Colo colon obedo lanyut ma pire tek pa UC. Kit ma ki nyutu kwede i cal 1D ki E, bor pa colon pa oyot ma gunongo DSS odok piny tutwal, ento ki kwanyo ki i yat BLG. Lacen, kitimo kwedo histonic me temo inflammation.H&E cal ma ki keto ki rwom me two onyutu ni tic ki DSS obalo yub me colonic ki okelo balo crypt, kun yat BLG odwoko piny balo crypt ki rwom me two (lanyut 1F ki G). Ki ngeyo ni, gwok pa BLG i rwom me 1 g/Kg onongo rom ki rwom me SASP20 mg/Kg. Ka ki keto kacel, gin ma kinongo ni nyutu ni BLG tiyo maber me dwoko piny pek pa two ma mako ic ma bino pi kare malac ma bino pi DSS i kom oyoo.
TNF-α, IL-1β ki IL-6 gubedo lanyut ma pire tek me kelo two i ic. Kit ma ki nyutu kwede i cal 2A, DSS okelo dongo ma pire tek i gene expression pa TNF-α, IL-1β ki IL-6 i ic ka kiporo ki gurup ma ki temo. Miyo BLG twero dwoko piny alokaloka magi ma DSS okelo, ma wa tiyo kwede me moko rwom me ELISA. cytokines ma kelo two TNF-α, IL-1β, ki IL-6 i kom ic. Adwogi ni bene onyutu ni rwom me TNF-α, IL-1β, ki IL-6 i ic omede matek i kom oyoo ma ki miyo bot gi DSS, kun yat BLG odwoko piny rwom me dongo eni (lanyut 2B).
cal me 2 BLG gengo nyutu pa gene ki yubu cytokines ma kelo two TNF-α, IL-1β ki IL-6 i ic pa oyot ma ki miyo igi DSS.(A) Nyutu pa gene pa TNF-α, IL-1β ki IL-6; (B) rwom me protein ma tye i ic pa TNF-α, IL-1β ki IL-6. Ngec ni ki nyutu calo rwom me ± SEM (n = 4–6).#p < 0.05 onyo ##p < 0.01 onyo ###p < 0.001 ki dul ma ki temo (Con); *p < 0.05 onyo **p < 0.01 ki dul pa DSS.
Peko me ic tye gin ma pire tek i dongo pa UC.24 Me kwedo ka BLG loko kit ma ic pa twol ma ki miyo bot gi DSS, 16S rRNA sequencing ki otimo me nyamo dul pa bacteria ma tye i ic. Labol me Venn nyutu ni gurup adek ni ginywako 385 OTUs. I kare acel, gurup acel acel onongo tye ki pat pat (OTUs. 3A).Medo ikom meno, Chao1 index ki Shannon index ma ki nyutu i cal 3B ki C onyutu ni dul ma pat pat pa gut microbiota odok piny i BLG-treated mice, ma calo Shannon index odok piny tutwal i BLG-treated group. Principal component analysis (PCA) ki principal coordinate analysis (PCA) ki tiyo kwede me moko pattern adek gurup ki onyutu ni dul pa oyot ma ki miyo igi DSS onongo opokke maber inge miyo kony me BLG (lanyut 3D ki E). Lok ma ki nongo ni nyutu ni BLG okelo alokaloka madit i kom dul pa oyot ma tye ki two ma ki lwongo ni DSS.
cal 3 BLG loko kit ma jami makwo ma i ic gi tye kwede i kom two ma ki lwongo ni DSS-induced colitis.(A) Venn diagram me OTU, (B) Chao1 index, (C) Shannon's richness index, (D) Principal Component Analysis (PCA) score plot of OTU, (E) OTU Principal Coordinate Analysis score (PCA) cal. Ngec ni ki nyutu calo rwom me ± SEM (n = 6).**p < 0.01 ki dul pa DSS.
Me temo alokaloka ma pat pat i kom jami makwo ma i ic, wa kwano kit ma jami makwo ma i ic gi tye kwede i rwom me poko kin jami weny. Kit ma ki nyutu kwede i cal 4A, dul ma pire tek i gurup weng obedo Firmicutes ki Bacteroidetes, ma lubo ki Verrucomicrobia. Wel Firmicutes ki Firmicutes/Bacteroidetes ma rwate i kom mon ma ki nywalo odongo matek dul ler ma ki lwongo ni DSS-treated mice ka kiporo ki control mice, ki alokaloka eni odok cen i nge miyo BLG. I kom lok, BLG omedo wel Verrucobacterium i ic pa oyot ma tye ki DSS-induced colitis. I rwom me gang, fecal microbial communities onongo ki gwoko ki Lachnoa, Muribaculaceae, Akkermansiaceae, Ruminococcaceae ki Prevotellaceae (Fig. 4B). Ka kiporo ki dul pa DSS, rwenyo pa BLG omedo wel pa Akkermansiaceae, ento odwoko piny wel pa Lachnospiraceae ki Ruminococcaceae i rwom ma lamal. ma ki gwoko ki Lachnospira_NK4A136_group, Akkermansia ki Prevotellaceae_UCG-001 (Fig. 4C). Gin ma kinongo ni bene onyutu ni tic ki BLG odwoko piny peko me microbiota i gamo peko me DSS, ma ki nyutu ki dwoko piny pa Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas ki Oscillibacter, ki medo pa Akkermansia ki Prevotellaceae_UCG-001.
cal me 4 BLG loko dwong pa jami ma kwo i ic i DSS-induced colitis mice.(A) dwong pa jami ma kwo i ic i rwom me phylum; (B) Pol pa jami ma kwo i ic i rwom me gang; (C) Wel microbiota ma tye i ic i rwom me dul kom. *p < 0.05 onyo **p < 0.01 onyo ***p < 0.001 ki dul pa DSS.
Ka kiporo ni short-chain fatty acids (SCFAs) gubedo jami ma kelo alokaloka madit i Akkermansia ki Prevotellaceae_UCG-001, ma nongo acetate, propionate ki butyrate gubedo SCFAs mapol loyo i lumen me ic, 25-27 pud wa tye i kwan wa. Kit ma ki nyutu kwede i cal 5, rwom me fecate, butyrate ki propiorate onongo odok piny tutwal i dul ma kimiyo bot gi DSS, ma nongo yat BLG onongo twero gengo dwoko piny man.
cal 5. BLG medo rwom pa SCFAs i ic pa oyot ma tye ki two ma ki lwongo ni DSS-induced colitis.(A) Acetic acid ma tye i ic; (B) rwom me propionic acid ma tye i ic; (C) butyric acid ma tye i ic. Lok ma ki nongo ki nyutu calo rwom me ± SEM (n = 6).#p < 0.05 onyo ##p < 0.01 ki dul ma ki temo (Con); *p < 0.05 onyo **p < 0.01 ki dul pa DSS.
Wa medo ki kwano Pearson correlation coefficient i kin genus-level differential SCFA ki fecal microbiota. Kit ma ki nyutu kwede i cal me 6, Akkermansia onongo tye ki rwate maber ki yubu pa propionic acid (Pearson = 0.4866) ki butyric acid (Pearson = 0.6192 I kom lok, Enteromonas ki Ocillocters onongo pe rwate). ma rwate ki yubu acetate, ki Pearson coefficients me 0.4709 ki 0.5104, kit meno. Kit meno bene, Ruminococcaceae_UCG-014 onongo tye ki rwate marac ki yubu propionic acid (Pearson = 0.4508) ki butyric acid (Pearson = 0.4508), kit meno.
cal 6 Pearson correlation analysis i kin SCFAs ma pat pat ki colonic microbes.(A) Enteromonas ki acetic acid; (B) Concussion bacillus ki acetic acid; (C) Akkermansia ki propionic acid; (D) Ruminococcus_UCG-014 ki propionic acid; (E) Akkermansia ki butyric acid; (F) ) Ruminococcus _UCG-014 ki butyric acid.
Glucagon-ma calo peptide-1 (GLP-1) tye gin ma ki lwongo ni cell-type-specific post-translational product pa proglucagon (Gcg) ma tye ki jami ma gengo two.28 Kit ma ki nyutu kwede i cal 7, DSS okelo dwoko piny ma pire tek i Gcg mRNA ma ki nyutu. Colon ki BLG ma ki miyo twero dwoko piny GSS ma ki dwoko piny ka kiporo ki dul ma ki temo (Fig. 7A).I kare acel, rwom pa GLP-1 i remo onongo odok piny tutwal i dul ma ki miyo iye DSS, ki BLG onongo twero gengo dwoko piny man (Fig. 7B). Kit ma short-chain fatty acids twero weko GLP-1 kato ki i G-protein-coupled receptor 43 (GRP43) ki GRP-protein-protein receptor (43) tic, wan bene wa temo GPR41 ki GRP43 i ic pa oyot ma tye ki two colitis ki wanongo ni colonic mRNA ma ki nyutu pa GRP43 ki GPR41 odok piny tutwal inge DSS challenge, ki yat BLG twero laro dwoko piny eni maber (lanyut 7C ki D).
cal 7 BLG medo rwom me GLP-1 i remo ki colonic Gcg, GPR41 ki GRP43 mRNA ma ki nyutu i DSS-treated mice.(A) Gcg mRNA ma ki nyutu i colon tissue; (B) rwom me GLP-1 i remo; (C) GPR41 mRNA ma ki nyutu i kom ic; (D) GPR43 mRNA ma ki nyutu i colon tissue. Data ki nyutu calo mean ± SEM (n = 5–6).#p < 0.05 onyo ##p < 0.01 vs control (Con) group; *p < 0.05 ki dul pa DSS.
Kit ma yat BLG twero medo rwom me GLP-1 i remo, nyutu pa Gcg mRNA i ic, ki rwom me SCFA i ic pa oyot ma ki miyo DSS, wa medo kwedo acetate, propionate, ki butyrate kacel ki ki i control (F-Con), DSS colitis (F-Con) -DSS) ki BLG-treated colitis (F-Con) ma ki gonyo i GLP-1 ki i kom ler ma ki lwongo ni primary murine colonic epithelial cells. Kit ma ki nyutu kwede i cal 8A, primary mouse colonic epithelial cells ma ki tiyo kwede ki 2 mM acetic acid, propionic acid, ki butyric acid, kit meno, okelo alokaloka madit i kom GLP-1, ma rwate ki kwan mukato.29,30 Kit meno bene, FDS-CON, ki F-BL-on, F-G-equivalent ( 0.25 g me feces) oweko ki gonyo GLP-1 ki i kom ler ma ki lwongo ni primary murine colonic epithelial cells. Ki ngeyo ni, wel GLP-1 ma ki gonyo ki F-DSS-treated primary mouse colonic epithelial cells onongo tye piny loyo pa F-Con ki F-BLG-treated primary mouse epithelial cells (Labol 8 B). Yat me BLG odwoko rwom me tic pa GLP-1 ma aa ki i ic.
cal 8 BLG-derived SCFA weko GLP-1 kato ki i kom ler ma ki lwongo ni primary murine colonic epithelial cells.(A) Acetic acid, propionic acid, ki butyric acid okonyo me gonyo GLP-1 ki i primary murine colonic epithelial cells; (B) jami ma ki kwanyo ki i ic F-Con, F-DSS ki F-BLG ma ki kwanyo ki ikom ler ma ki lwongo ni murine colonic epithelial cells Wel GLP-1 ma ki gonyo.Aliquots pa colonic epithelial cells ki keto gi i glass-bottom petri dishes ki ki tiyo kwede ki 2 mM acetic acid, propionic acid, propioric acid, but fecal extract, ki F-Con F-DSS, ki F-BLG (ma rom ki 0.25 g me feces), kit meno. 2 cawa i 37°C, 5% CO2, kit meno. Wel pa GLP-1 ma ki gonyo ki i kom ler ma ki lwongo ni primary murine colonic epithelial cells ki nongo ki ELISA. Data ki nyutu calo mean ± SEM (n = 3).#p < 0.05 onyo ##p < 0.01 vs. blank or F-C on; *p < 0.05 ki F-DSS.
Lok ma ki coyo macek: Ace, acetic acid; Pro, propionic acid; kadi bed kumeno, butyric acid; F-Con, gin ma ki kwanyo ki i kom oyoo ma ki temo; F-DSS, gin ma ki kwanyo ki i kom oyot ma tye ki two colitis; F-BLG, ki i BLG-treated colon Fecal extracts of inflammatory mice.
Ki keto i kin two ma ki lwongo ni World Health Organization calo two ma pe cang, UC tye ka dugu peko i wilobo weny; kadi bed kumeno, yoo maber me ngeyo, gengo, ki cango two ni pud nok. Pi meno, tye gin ma mite oyotoyot me yenyo ki yubu yoo manyen me cango two UC. Yat me tekwaro pa jo China tye yoo maber pien yadi me tekwaro pa jo China mapol dong ki nyutu ni tiyo maber i cango two UC i kin dano mapol, ki gin weng obedo jami makwo ki jami ma kicweyo ma pol kare pe kelo peko i kom dano ki lee.31,32 Kwano man onongo tye me yenyo yoo me cango two ma ki lwongo ni UC ki me temo kit ma en tiyo kwede.BLG obedo yadi ma ki ngeyo maber ma ki tiyo kwede me cango two ma kobo. yadi me tekwaro pa jo China ma aa ki i kom jami ma ki yubu ki BLG, nyutu tic maber i cango two UC i kom dano ki lee.4,34 Ento, adwogi pa BLG i kom two ma mako ic ki adwogi ne pe tye atir. I kwan ma tye ka time ni, adwogi wa nyutu ni BLG dwoko piny two ma bino pi DSS, ma rwate ki loko ic microbiota ki dwoko cen GLP-1 ma aa ki i ic.
Ki ngeyo maber ni UC ki nyutu ki kare ma dwogo cen ki jami ma nen, ma calo rwenyo pek pa kom, cado, remo ma aa ki i ic, ki balo ic madwong.35 Pi meno, two ma mako ic ma dwogo cen ki miiyo ki miiyo nino adek me 1.8% DSS pi nino abic, ki lubo ki mato pii i nino abiro ma ki nyutu i cal.A. 1B, rwenyo pek pa kom ki rwom me DAI onyutu ni otiime maber me kelo two ma mako ic. Otwo ma ki miyo igi yat ki BLG onyutu ni gi dwoko rwom me kwo gi piny ki i nino me 8, ma onongo pat ki nino me 24. Alokaloka acel-lu bene ki neno i rwom me DAI, ma nyutu ni rwom me dongo pa two ma mako ic ki two ma mako ic odongo. bor pa ic, balo kom ic, ki nyutu gene ki yubu cytokines ma kelo two TNF-α, IL-1β, ki IL-6 i kom ic bene odongo maber inge yat BLG. Ka ki keto kacel, adwogi eni nyutu ni BLG tiyo maber i cango two ma mako ic ma bino pi kare malac.
BLG tiyo ki adwogi me cango two nining? Kwan mapol mukato angec onyutu ni jami makwo ma i ic gi tiyo tic ma pire tek i kelo two UC, ki yoo me cang ma jenge i kom jami makwo ki jami makwo ma ki lwongo ni microbiome okati calo yoo maber me cango two UC. I kwan ma tye i kare ni, wanyutu ni yat BLG okelo alokaloka madit i kit ma ic tye kwede gwok pa BLG i kom two ma ki lwongo ni DSS-induced colitis tye ki rwate ki loko kit ma ic microbiota tiyo kwede. Neno man rwate ki tam ni loko kit ma gut microbiota tiyo kwede obedo yoo ma pire tek me niang kit ma TCM tiyo kwede.36,37 Ki ngeyo ni, Akkermansia tye Gram-negative ki strictly anaerobicus ma kwo i layer me lac gut, ma balo mucins, kelo propionic acid, weko goblet cell poko kin gii, ki gwoko mucosa. tic pa jami ma gengo.26 Lok mapol ma ki nongo ki i ot yat ki lee nyutu ni Akkermansia tye ki rwate ki mucosa ma yot,38 ki miyo Akkermansia spp. twero dwoko piny rwom me pong pa remo.39 Lok ma kinongo i kare ni nyutu ni wel pa Akkermansia omede i nge yat BLG. Medo ikom meno, Prevotellaceae_UCG-001 obedo kwidi ma kelo SCFA.27 Kwan mapol onyutu ni Prevotellaceae_UCG-001 onongo tye i wel ma nok i kom ler colitis.40,41 Lok ma wa tye kwede i kare ni bene nyutu ni yat ma ki lwongo ni BLG twero medo rwom me Prevotellaceae_UCG-001 i ic pa oyot ma ki miyo igi DSS. I apoka poka, Oscillibacter obedo mesophilic, ma pe tiyo ki yamo.42 owaco ni rwom me Ocillibacter omede i UCCliter oyot ki onongo tye ki rwate maber ki IL-6 ki IL-1β ki rwom me two.43,44 Ki ngeyo, yat BLG odwoko piny wel pa Oscillibacter i ic pa oyot ma ki miyo DSS. Ki ngeyo, BLG-altered bacteria magi aye gubedo SCFA-produmer ma kelo adwogi maber loyo i kom kwan macon. SCFAs i kom colonic inflammation ki gwoko intestinal epithelial integrity.45,46 Ngec ma wa tye kwede i kare ni bene onyutu ni dwong pa SCFA acetate, propionate, ki butyrate i DSS-treated feces onongo tye ka medde matek i BLG-treated mice. SCFA-producing bacteria i kom oyoo ma tye ki two ma mako ic ma bino pi kare malac.
GLP-1 obedo gin ma ki lwongo ni incretin ma ki yubu i ileum ki colon ki tiyo tic ma pire tek me juku yweyo pa ic ki dwoko piny cukari ma i remo i nge cam.47 Gin ma ki nongo nyutu ni dipeptidyl peptidase (DPP)-4, gin ma gengo GLP-1 receptor, ki GLP-1 nanomedicine twero konyo me juku two ma mako ic. ma ki waco i kwan mukato, dwong pa SCFA onongo tye ka rwate ki dwong pa GLP-1 i remo pa dano ki oyoo. 52 Ngec ma wa tye kwede i kare ni nyutu ni inge yat BLG, rwom me GLP-1 i remo ki nyutu pa Gcg mRNA omede matek. I yo acel-lu, GLP-1 ma ki cwalo omede i colonic cultures ma lubo tic ki jami ma ki kwanyo ki i BLG-treated colitis mice ka kiporo ki tic ki fecal extracts ki i DSS-treated colitis mice. gonyo GLP-1?Gwen Tolhurst et al. owaco ni SCFA twero juku tic pa GLP-1 kun wok ki i GRP43 ki GPR41.29 Ngec ma wa tye kwede i kare ni bene nyutu ni tic ki BLG medo rwom me mRNA pa GRP43 ki GPR41 i colon pa oyot ma ki miyo DSS. Ngec man nyutu ni tic ki BLG twero dwoko cen GLP-1 ma ki kelo ki GRP444443.
BLG obedo yadi ma ki wilo pi kare malac (OTC) i lobo China. Kit ma ki miiyo kwede BLG i Kunming mice tye 80g/Kg, ki pe ki neno ni tye ki peko mo.53 I kare ni, kit ma ki miiyo kwede BLG (labongo cukari) i kom dano tye 9-15 g/day (tyen 3 i nino acel acel). Kwano wa onyutu ni BLG i 1g/DSS okonyo me kelo two ma mako two ma mako wic i kom oyot. Yat man cok ki yat me BLG ma kitiyo kwede i ot yat. Kwano wa bene onongo ni kit ma en tiyo kwede ki kelo, i dul mo, ki alokaloka i gut microbiota, ma loyo SCFA-producing bacteria, calo Akkermansia ki Prevotellaceae_UCG-001, me dwoko cen GLP-derived gut-derived production. medo ki neno calo gin ma twero konyo me cango two ma mako ic. Ento, kit ma en loko kwede jami makwo ma i ic pwod pe ki moko ki i kom oyot ma pe ki jami ma kwo i ic ki jami ma ki keto i ic.
Ace, acetic acid; ento, butyric acid; BLG, pandan; DSS, dextran sodium sulfate; DAI, lanyut me tic pa two; DPP, dipeptidyl peptidase; FID, gin ma nyutu ka mac tye ka lyel; F-Con, gwoko jami ma ki kwanyo ki i kom oyoo; F-DSS, gin ma ki kwanyo ki i kom two ma ki lwongo ni DSS colitis mice; F-BLG, gin ma ki kwanyo ki i kom two ma ki lwongo ni BLG-treated colitis mice; GLP-1, glucagon-ma calo peptide-1; Gcg, glucagon; jami ma ki lwongo ni 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, jami ma pire tek ma ki kwano; PCoA, gin ma ki lwongo ni principal coordinate analysis; Pro, propionic acid; SASP, sulfasalazine; SCFA, short-chain fatty acids; Yat pa jo China, yadi pa jo China macon; UC, two ma mako ic.
Cik me temo ni weng ki yee ki komiti ma neno kit ma ler tye kwede i University me Peking Shenzhen-Hong Kong University of Science and Technology Medical Center (Shenzhen, China) malube ki cik ma kwako ler (namba me kit maber A2020157).
Lucoc weny gu miiyo kony ma pire tek i kom tam ki yubu, nongo ngec, onyo nyamo ki gonyo ngec; onywako i coyo lok ma ki coyo ni onyo loko jami ma pire tek ma ki coyo ni; oyee me cwalo waraga ni bot magazin ma tye ka tic i kare ni; i agiki oyee ni ki coc ne; Tye ki twero i kom jami weny ma mako tic.
Tic man onongo kony ki bot National Natural Science Foundation of China (81560676 ki 81660479), yub me rwom ma malo pa Shenzhen University (86000000210), Shenzhen Science and Technology Innovation Committee Fund (JCYJ202103240938102010), ki Guangdong Science and Medical Science lim me kwedo ngec (A2020157 ki A2020272), Guizhou Medical University Pharmacy Guizhou Province ma ki miiyo cente ki Key Laboratory (YWZJ2020-01) ki Peking University Shenzhen Hospital (JCYJ2018009).
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