基于FXR/SHP/PEPCK和FXR/ApoCⅡ通路探讨茵陈五苓散对代谢相关脂肪性肝病大鼠糖脂代谢的作用  

Effects of Yinchen Wuling powder on glycolipid metabolism in metabolic associated fatty liver disease rats based on FXR/SHP/PEPCK and FXR/ApoCⅡ pathways

作　　者：石丹丹 艾碧琛[1] 李木兰 张毅[1] 刘杰[1] SHI Dandan;AI Bichen;LI Mulan;ZHANG Yi;LIU Jie(Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208

出　　处：《陕西中医》2025年第2期153-158,共6页Shaanxi Journal of Traditional Chinese Medicine

基　　金：湖南省教育厅科研基金资助重点项目(18A215);湖南省中医药管理局科研计划项目(D2022016);湖南中医药大学中医学一流学科开放基金资助项目(2022ZYX09);湖南中医药大学研究生创新立项课题(2023CX174)。

摘　　要：目的:基于法尼醇X受体(FXR)/微小异源二聚体(SHP)/磷酸烯醇式丙酮酸羧激酶(PEPCK)和FXR/载脂蛋白CⅡ(ApoCⅡ)通路探讨茵陈五苓散对代谢相关脂肪性肝病(MAFLD)大鼠糖脂代谢的作用。方法:用高脂饮食建立MAFLD大鼠模型,将成模大鼠随机分为模型组、茵陈五苓散高剂量组、茵陈五苓散低剂量组和辛伐他汀组,并选取同批次未进行造模处理的大鼠作为空白组。各组给予相应药物和0.9%氯化钠溶液干预4周。灌胃期间每周定时检测各组大鼠的体重和空腹血糖(FBG);生化法检测总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、谷丙氨酸氨基转移酶(ALT)及天冬氨酸氨基转移酶(AST)水平;ELISA法检测胰岛素(FINS)水平,并计算胰岛素抵抗指数(HOMA-IR);HE染色进行肝脏组织病理学观察;RT-qPCR法检测肝脏FXR、SHP、PEPCK、ApoCⅡmRNA水平。结果:与模型组比较,茵陈五苓散高剂量组、茵陈五苓散低剂量组和辛伐他汀组体重、肝重和肝指数明显降低(P<0.05);FBG、FINS和HOMA-IR水平明显降低(P<0.05);血清TG、TC、LDL-C、AST、ALT含量明显降低,HDL-C含量升高(P<0.01);肝组织结构均有不同程度的改善(P<0.01);FXR、SHP、ApoCⅡmRNA表达增加(P<0.01),PEPCK mRNA表达减少(P<0.01)。结论:茵陈五苓散能够改善MAFLD大鼠糖脂代谢紊乱和肝脏组织病理状态,其机制可能与调节FXR/SHP/PEPCK和FXR/ApoCⅡ通路有关。Objective:To explore the effects of Yinchen Wuling powder on glycolipid metabolism in rats with metabolism-associated fatty liver disease(MAFLD)based on the farnesol X receptor(FXR)/small heterodimer protein(SHP)/phosphoenolpyruvate carboxykinase(PEPCK)and FXR/apolipoprotein CⅡ(ApoCⅡ)pathways.Methods:The MAFLD rat model was established with high-fat diet,and the rats with successful modeling were randomly divided into the model group,Yinchen Wuling powder high-dose group,Yinchen Wuling powder low-dose group and simvastatin group,and the same batch of non-modeling rats were selected as the blank group.Each group was given the corresponding drugs and saline intervention for 4 weeks.During the gavage period,the body mass and fasting blood glucose(FBG)of the rats in each group were measured regularly every week;the biochemical methods were used to determine the levels of total cholesterol(TC),triglycerides(TG),high density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT)and aspartate transaminase function(AST);ELISA to detect fasting serum lisulin(FINS)levels and calculate Homeostatic Model Assessment for Insulin Resistance(HOMA-IR);HE staining for histopathological observation of the liver;RT-qPCR to detect hepatic FXR,SHP,PEPCK,and ApoCⅡmRNA levels.Results:Compared with the model group,the body weight,liver weight and liver index were significantly reduced in the Yinchen Wuling powder high-dose group,Yinchen Wuling powder low-dose group and simvastatin group(P<0.05);FBG,FINS and HOMA-IR levels were significantly reduced(P<0.05);serum TG,TC,LDL-C,AST and ALT levels were significantly decreased,and HDL-C levels were increased(P<0.01);liver tissue structure was improved to varying degrees(P<0.01);FXR,SHP,ApoCⅡmRNA expression increased(P<0.01),PEPCK mRNA expression decreased(P<0.01).Conclusion:Yinchen Wuling powder was able to ameliorate the disorders of glucose-lipid metabolism and liver histopathology in MAFLD rats,and its mechanism may be related to the

关 键 词：代谢相关脂肪性肝病 茵陈五苓散 糖代谢 脂代谢 法尼醇X受体 通路 

分 类 号：R575.5[医药卫生—消化系统]