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异甘草素调控肠道菌群和肠屏障功能改善小鼠非酒精性脂肪性肝病的作用机制
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| 篇名： | 异甘草素调控肠道菌群和肠屏障功能改善小鼠非酒精性脂肪性肝病的作用机制 |
| TITLE： | The mechanism of isoliquiritigenin on ameliorating non-alcoholic fatty liver disease in mice by regulating gut microbiota and repairing gut barrier function |
| 摘要： | 目的 研究异甘草素对高脂饮食诱导的非酒精性脂肪性肝病（NAFLD）模型小鼠肠道菌群和肠屏障功能的调控作用，阐明其改善NAFLD的机制。方法将30只雄性C57BL/6J小鼠随机分为正常组（超纯水）、模型组（超纯水）和异甘草素组（100mg/kg），每组10只。模型组和异甘草素组喂食高脂饲料19周建立NAFLD模型；造模同时，各组小鼠灌胃相应药物/超纯水。记录各组小鼠体重变化，计算小鼠肝指数、白色脂肪指数和棕色脂肪指数；观察小鼠肝脏组织和结肠组织的病理变化以及肝脏脂质堆积情况；检测小鼠血清或肝脏中总胆固醇（TC）、甘油三酯（TG）、天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平；检测小鼠血清中白细胞介素6（IL-6）、IL-1β和肿瘤坏死因子α（TNF-α）水平和肝脏组织中IL-6、IL-1β、TNF-αmRNA表达水平；取小鼠粪便进行16SrRNA测序，考察异甘草素对模型小鼠肠道菌群结构的影响；检测小鼠结肠组织中肠黏膜屏障功能相关蛋白[闭合蛋白4（Claudin-4）、闭合蛋白（Occludin）、紧密连接蛋白1（ZO-1）]的表达水平。结果与模型组比较，异甘草素组小鼠体重、肝指数，肝脏和血清中TC水平以及血清中AST、ALT水平，血清中IL-6、IL-1β和TNF-α水平，肝脏组织中TNF-αmRNA表达水平均显著降低；棕色脂肪指数显著升高；肝脏组织炎症与损伤显著改善，NAFLD活动评分和脂质染色面积占比均显著减少（P＜0.05）。异甘草素可显著上调小鼠肠道益生菌（norank_f_Muribaculaceae、Odoribacter、Ruminiclostridium等）的相对丰度以及肠黏膜屏障功能相关蛋白表达水平，显著下调有害菌（Desulfovibrio、norank_f_Lachnospiraceae、unclassified_p_Firmicutes等）的相对丰度，修复肠黏膜屏障。结论异甘草素可显著延缓NAFLD的进展，其作用机制可能与调节肠道菌群、改善肠屏障功能有关。 |
| ABSTRACT： | OBJECTIVE To study the effects of isoliquiritigenin （ISL） regulating gut microbiota and repairing gut barrier function in model mice with non-alcoholic fatty liver disease （NAFLD）， and to clarify its mechanism for improving NAFLD. METHODS Thirty male C57BL/6J mice were randomly divided into the normal （ultrapure water）， model group （ultrapure water）， ISL group （100 mg/kg）， with 10 mice in each group. Model group and ISL group were fed with high-fat diet for 19 weeks to establish NAFLD model； at the same time， the mice were given relevant medicine/ultrapure water intragastrically. The changes of body weight in mice were recorded， and liver index， white fat index and brown fat index were calculated. The pathological changes of liver tissue and colon tissue as well as lipid accumulation were observed in mice. The levels of total cholesterol （TC）， triglyceride （TG）， aspartate aminotransferase （AST） and alanine aminotransferase （ALT） E-mail：xiangshj3@mail.sysu.edu.cn in serum or liver were measured； the serum levels of interleukin-6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α） and the levels of IL-6， IL-1β and TNF-α mRNA expression in liver tissue were detected. Fecal samples underwent 16S rDNA sequencing analysis， and the effects of ISL on gut microbiota structure of mice were investigated. The expressions of gut mucosal barrier-related proteins （Claudin-4， Occludin and ZO-1） were determined in the colon tissue of mice. RESULTS Compared with model group， the body weight， liver index， the levels of TC in liver tissue and serum， the levels of AST and ALT in serum， the levels of IL-6， IL-1β and TNF-α in serum， and the mRNA expression of TNF-α in liver tissue were all decreased significantly in ISL group， while brown fat index was increased significantly. The inflammation and damage of liver tissue were significantly improved， and the NAFLD activity score and the proportion of lipid staining area were significantly reduced （P＜0.05）. ISL could significantly up-regulate the relative abundance of beneficial microbiota （norank_f_Muribaculaceae， Odoribacter， Ruminiclostridium， etc.） and the expressions of intestinal barrier function- related proteins， but could significantly down-regulate the relative abundance of harmful bacteria （Desulfovibrio， norank_f_Lachnospiraceae， unclassified_p_Firmicutes）， and could repair intestinal barrier. CONCLUSIONS ISL could significantly delay the progress of NAFLD， the mechanism of which may be associated with regulating gut microbiota and improving gut barrier function. |
| 期刊： | 2023年第34卷第23期 |
| 作者： | 曾海燕；简丽娜；吴辉星；周本杰；乡世健 |
| AUTHORS： | ZENG Haiyan，JIAN Lina，WU Huixing，ZHOU Benjie，XIANG Shijian |
| 关键字： | 异甘草素；肠道菌群；肠黏膜屏障；非酒精性脂肪性肝病 |
| KEYWORDS： | isoliquiritigenin； gut microbiota； gut mucosal barrier； non-alcoholic fatty liver disease |
| 阅读数： | 26 次 |
| 本月下载数： | 2 次 |
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