苍菊清肝降脂方对代谢相关脂肪性肝病小鼠胆汁酸代谢的影响及机制OACHSSCD
Effects and Mechanisms of Cangju Qinggan Jiangzhi Formula on Bile Acid Metabolism in Mice with Metabolic Dysfunction-associated Steatotic Liver Disease
目的:探讨苍菊清肝降脂方对代谢相关脂肪性肝病(MASLD)小鼠肝损伤及胆汁酸代谢的影响.方法:40只C57BL/6J小鼠按照随机数字表法分为对照组、模型组、奥贝胆酸组和苍菊清肝降脂方低、高剂量组(2.3、4.6 g/kg),采用高脂饮食喂养16周建立MASLD模型.检测各组小鼠体质量、肝湿重、肝功能与血脂以及肝组织三酰甘油含量;苏木精-伊红染色和油红O染色评估肝组织病理学改变;超高效液相色谱-串联质谱技术检测肝脏、血清和粪便胆汁酸谱,实时荧光定量聚合酶链式反应和蛋白质印迹法分别检测法尼醇X受体(FXR)、小异二聚体伴侣蛋白(SHP)、胆固醇7α-羟化酶(CYP7A1)、固醇27-羟化酶(CYP27A1)、胆汁盐输出泵(BSEP)、钠-牛磺胆酸协同转运多肽(NTCP)的信使核糖核酸(mR-NA)和蛋白表达情况.结果:与对照组比较,模型组小鼠体质量、肝湿重、肝功能以及血脂水平明显升高(P＜0.05),肝脏和血清多种胆汁酸蓄积、粪便胆汁酸排泄减少(P＜0.05),FXR、SHP、BSEP mRNA和蛋白表达下调(P＜0.05),CYP7A1、NTCP mRNA和蛋白表达上调(P＜0.05).与模型组比较,不同剂量苍菊清肝降脂方干预后,小鼠上述指标均明显改善(P＜0.05).结论:苍菊清肝降脂方可缓解MASLD小鼠肝损伤,改善胆汁酸代谢失衡,其作用机制可能与调控FXR/SHP介导的胆汁酸合成与转运相关通路有关.
Objective:To investigate the effects of Cangju Qinggan Jiangzhi Formula on hepatic injury and bile acid metabolism in mice with metabolic dysfunction-associated steatotic liver disease(MASLD).Methods:Forty C57BL/6J mice were randomly divid-ed into a control group,a model group,an obeticholic acid group,and low-and high-dose Cangju Qinggan Jiangzhi Formula groups(2.3 and 4.6 g/kg)according to a random number table.A MASLD model was established by feeding a high-fat diet for 16 weeks.Body weight,liver wet weight,liver function indices,serum lipid levels,and hepatic triglyceride content were measured.His-topathological changes in liver tissue were evaluated using hematoxylin-eosin(HE)staining and Oil Red O staining.Bile acid pro-files in liver,serum,and feces were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry(UH-PLC-MS/MS).The mRNA and protein expression levels of farnesoid X receptor(FXR),small heterodimer partner(SHP),choles-terol 7α-hydroxylase(CYP7 A1),sterol 27-hydroxylase(CYP27 A1),bile salt export pump(BSEP),and sodium taurocholate co-transporting polypeptide(NTCP)were detected by quantitative real-time PCR(qRT-PCR)and Western blot,respectively.Results:Compared with the control group,the model group showed significant increases in body weight,liver wet weight,liver function indi-ces,and serum lipid levels(P＜0.05),accompanied by accumulation of multiple bile acids in the liver and serum and decreased bile acid excretion in feces(P＜0.05).The mRNA and protein expression levels of FXR,SHP,and BSEP were downregulated(P＜0.05),whereas CYP7 A1 and NTCP were upregulated(P＜0.05).Compared with the model group,intervention with different doses of Cangju Qinggan Jiangzhi Formula significantly improved the above indices in mice(P＜0.05).Conclusion:Cangju Qinggan Jiangzhi Formula alleviates hepatic injury and improves bile acid metabolic imbalance in MASLD mice,and its mechanism may be associated with regulation of FXR/SHP-mediated pathways involved in bile acid synthesis and transport.
刘有芳;金源源;石杰文;陈建杰;成扬
上海中医药大学附属曙光医院肝病研究所,上海,201203||上海中医药大学,上海,200032上海中医药大学附属曙光医院肝病研究所,上海,201203||上海中医药大学,上海,200032上海中医药大学附属曙光医院肝病研究所,上海,201203||上海中医药大学,上海,200032上海中医药大学附属曙光医院肝病研究所,上海,201203上海中医药大学附属曙光医院肝病研究所,上海,201203
医药卫生
苍菊清肝降脂方代谢相关脂肪性肝病胆汁酸代谢法尼醇X受体信号通路小异二聚体伴侣蛋白胆汁酸转运蛋白肝脏脂质沉积中医药干预
《世界中医药》 2026 (9)
1677-1688,12
国家自然科学基金面上项目(81774098).
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