灯盏花乙素调节AMPK/SIRT1/PGC-1ɑ信号通路对溃疡性结肠炎大鼠肠道菌群的影响  

Regulatory effect of Scutellarin B on the gut microbiota of ulcerative colitis rats by regulating AMPK/SIRT1/PGC-1ɑ signaling pathway

作　　者：吴军城 赵立国 张立文 WU Juncheng;ZHAO Liguo;ZHANG Liwen(Digestive Endoscopy,Boao Yiling Life Care Center,Qionghai 571400,Hainan,China)

机构地区：[1]博鳌一龄生命养护中心消化内镜,海南琼海571400

出　　处：《中国病原生物学杂志》2024年第1期36-41,共6页Journal of Pathogen Biology

摘　　要：目的 探究灯盏花乙素(SCU)调节腺苷酸激活蛋白激酶(AMPK)/沉默调节蛋白1(SIRT1)/过氧化物酶体增殖活化受体γ辅助活化因子1α(PGC1α)信号通路对溃疡性结肠炎(UC)大鼠肠道菌群的影响。方法 随机选择6只SD大鼠作为空白对照组(NC组),另取24只腹腔注射3.5%葡聚糖硫酸钠(DSS)构建UC大鼠模型。将UC大鼠随机平分为UC组、SCU组(100 mg/kg)、Compound C组(AMPK/SIRT1/PGC-1ɑ信号通路抑制剂Compound C 250μg/kg体重)以及SCU+Compound C组(SCU100 mg/kg体重+250μg/kg体重Compound C),NC组、UC组给予等量生理盐水。每组均6只大鼠。ELISA法检测血清炎性因子水平;HE染色观察结肠组织病理学变化;对粪便进行短链脂肪酸(SCFAs)测序以及16s测序,并进行序列分析;Western blot检测AMPK/SIRT1/PGC-1ɑ信号通路蛋白表达水平。结果 NC组大鼠结肠绒毛形态完整,结肠黏膜上皮结构清晰可见,肠腺内多个细胞整齐排列,无任何病变。与NC组相比,UC组大鼠结肠组织隐窝和杯状细胞消失,炎症细胞浸润增加,乙酸盐、丙酸盐、丁酸盐含量,Shannon、Simpson、Chao1指数,乳酸杆菌属相对丰度及AMPK、SIRT1、PGC1α水平均显著降低(均P<0.05);IL-1β、TNF-α、IL-6水平,大肠埃希菌-志贺菌属及拟杆菌属相对丰度显著升高(均P<0.05)。与UC组相比,SCU组粘膜结构以及炎性细胞浸润现象得到改善,粘膜结构基本完整,杯状细胞数量显著增多;乙酸盐、丙酸盐、丁酸盐含量,Shannon、Simpson、Chao1指数,乳酸杆菌属相对丰度及AMPK、SIRT1、PGC1α水平均显著增加(均P<0.05);IL-1β、TNF-α、IL-6水平,大肠埃希菌-志贺菌属及拟杆菌属相对丰度均显著减少(均P<0.05)。Compound C组上述指标变化趋势与SCU组比较均相反。结论 SCU可通过激活AMPK/SIRT1/PGC-1ɑ信号轴升高有益菌的丰度,降低致病菌,改善UC大鼠肠道菌群失衡,减轻UC的炎症状态,发挥对UC的治疗作用。Objective To investigate the effect of Scutellarin B(SCU)on the gut microbiota of ulcerative colitis(UC)rats by regulating the adenosine monophosphate-activated protein kinase(AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α)signaling pathway.Methods Six SD rats were randomly selected as blank control group(NC group),and another 24 rats were intraperitoneally injected with 3.5%sodium dextran sulfate(DSS)to construct UC rat model.UC rats were randomly divided into UC group,SCU group(100 mg/kg),Compound C group(AMPK/SIRT1/PGC-1ɑsignaling pathway inhibitor Compound C 250μg/kg body weight),and SCU+Compound C group(SCU 100 mg/kg body weight+250μg/kg body weight Compound C),NC group and UC group were given equal amounts of physiological saline.There were 6 rats in each group.ELISA method was used to detect serum inflammatory factor level;HE staining was used to observe the histopathological changes of colon tissue;short chain fatty acid(SCFAs)sequencing and 16s sequencing were performed on feces and sequence analysis was performed;Western blot was used to detect the expression level of AMPK/SIRT1/PGC-1ɑsignaling pathway proteins.Results The morphology of colonic villi in NC group was intact,and the epithelial structure of colonic mucosa was clearly visible,multiple cells in the intestinal glands were neatly arranged without any lesions.Compared with the NC group,the crypts and goblet cells in the colonic tissue of UC group disappeared,and the infiltration of inflammatory cells increased,the contents of acetate,propionate,and butyrate,the indexes of Shannon,Simpson,and Chao1,the relative abundance of Lactobacillus,and the levels of AMPK,SIRT1,and PGC1 were significantly decreased(P<0.05),the levels of IL-1β,TNF-α,IL-6,and the relative abundances of Escherichia coli Shigella and Bacteroidetes were significantly increased(P<0.05).Compared with UC group,the SCU group had improved the mucosal structure and inflammatory cell infiltration were improved,,the mucosal structure was

关 键 词：灯盏花乙素 AMPK/SIRT1/PGC-1ɑ信号通路 肠道菌群 溃疡性结肠炎 

分 类 号：R285.5[医药卫生—中药学]