基于肠道菌群-胆汁酸代谢途径探讨芩连红曲汤对高脂血症大鼠的改善作用  

Qinlian Hongqu(芩连红曲) Decoction Ameliorates Hyperlipidemia in Rats via the Gut Microbiota-Bile Acid Metabolism Pathway

作　　者：杨炀[1] 赵美 罗雅琪[1] 郭志清[3] 张赣 何蕴良 陈东辉[1] 张钟艺 张树森 张永 YANG Yang;ZHAO Mei;LUO Yaqi;GUO Zhiqing;ZHANG Gan;HE Yunliang;CHEN Donghui;ZHANG Zhongyi;ZHANG Shusen;ZHANG Yong(Institute of Traditional Chinese Medicine,Sichuan Academy of Chinese Medicine Sciences(Sichuan Second Hospital of Traditional Chinese Medicine),Chengdu 610031;School of Basic Medical Sciences,Chengdu University of Traditional Chinese Medicine,Chengdu 611137;Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075;The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001)

机构地区：[1]四川省中医药科学院中医研究所(四川省第二中医医院),成都610031 [2]成都中医药大学基础医学院,成都611137 [3]成都中医药大学附属医院,成都610075 [4]贵州中医药大学第二附属医院,贵阳550001

出　　处：《中药药理与临床》2025年第1期33-38,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：四川省科技厅中央引领地方项目(编号:2023ZYD0049);四川省科技厅省级科研院所基本科研业务费项目(编号:2022JDKY0029);四川省中医药管理局中医药专项课题(编号:2023MS191)。

摘　　要：目的:研究芩连红曲汤对高脂血症的疗效及机制。方法:SD大鼠随机分成正常大鼠和模型大鼠,采用高脂饲料喂养造模12 w,造模成功后将模型大鼠随机分为模型对照组、芩连红曲汤0.7、1.4 g/kg组和阳性药阿托伐他汀1.05 g/kg组,每组6只。观察大鼠治疗前后体质量变化;采用生化法检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)及肝脏TC、TG含量;HE和油红O染色分别观察肝脏病理和脂质沉积情况;微生物16S生物信息分析观察大鼠肠道菌群情况;靶向胆汁酸代谢组学观察大鼠肠道内容物胆汁酸代谢物的变化。结果:与正常对照组比较,模型对照组大鼠体质量增加,血清TC、TG、LDL-C含量和肝脏TC、TG和FFA含量显著升高,肝脏出现脂肪样变及大量脂滴(P<0.01);与模型对照组比较,芩连红曲汤各组大鼠体质量减轻,血脂降低,肝脏病理学显示大鼠肝脏脂质沉积减轻,脂滴显著减少(P<0.01)。肠道菌群结果显示组间群落结构差异显著,厚壁菌门、拟杆菌门和变形杆菌在各组大鼠肠道菌群中占主导,与正常对照组相比,模型对照组中厚壁菌门丰度显著上升,拟杆菌门丰度显著下降(P<0.01);与模型对照组相比,芩连红曲汤1.4 g/kg组的厚壁菌门丰度下降,拟杆菌门丰度上升,逆转厚壁菌门/拟杆菌门(F/B)比值降低(P<0.01)。肠道内容物靶向代谢组学结果显示芩连红曲汤能促进胆汁酸的排泄。结论:芩连红曲汤可以改善大鼠高脂血症,其机制可能与肠道菌群-胆汁酸代谢通路有关。Objective:To study the therapeutic effect of Qinlian Hongqu(芩连红曲) Decoction on hyperlipidemia and decipher the treatment mechanism. Methods:SD rats were randomly assigned into blank control and modeling groups, and those in the modeling group were fed with a high-fat diet for 12 weeks. The successfully modeled rats were randomly assigned into model control, Qinlian Hongqu Decoction(0.7 and 1.4 g/kg),and positive drug(atorvastatin, 1.05 g/kg) groups, with 6 rats in each group. The changes in body weight before and after treatment were measured. Biochemical methods were used to measure the levels of total cholesterol(TC),triglycerides(TG),and low-density lipoprotein-cholesterol(LDL-C) in the serum as well as the levels of TC and TG in the liver. Hematoxylin-eosin(HE) staining and oil red O staining were employed to observe the pathological changes and lipid deposition, respectively, in the liver. The 16S rRNA sequencing was employed to analyze the gut microbiota of rats, and targeted bile acid metabolomics was employed to observe the changes of bile acid metabolites in the gut contents of rats. Results:Compared with the blank control group, the model control group showed increased body weight, elevated levels of TC,TG,and LDL-C in the serum and TC,TG,and free fatty acids(FFA) in the liver, steatosis, and a large number of lipid droplets in the liver tissue. Compared with the model control group, Qinlian Hongqu Decoction reduced the body weight, blood lipid levels, and lipid deposition and lipid droplets in the liver. The gut microbiota structure showed significant differences between groups, with Firmicutes, Bacteroidetes, and Proteobacteria being dominant. Compared with the normal control group, the model control group showed increased relative abundance of Firmicutes and decreased relative abundance of Bacteroidetes. Compared with the model control group, Qinlian Hongqu Decoction(1.4 g/kg) decreased the relative abundance of Firmicutes and increased the relative abundance of Bacteroidetes, reversing the F

关 键 词：芩连红曲汤 高脂血症 肠道菌群 胆汁酸 

分 类 号：R285.5[医药卫生—中药学]