金丝桃苷调节非酒精性脂肪性肝病大鼠脂质代谢的作用机制研究  

Mechanism of action of hyperoside in regulating lipid metabolism in rats with non⁃alcoholic fatty liver disease

作　　者：郅音 马星 张苗[1] 叶颖[1] 夏伟[1] 宋雅楠[1] ZHI Yin;MA Xing;ZHANG Miao;YE Ying;XIA Wei;SONG Ya'nan(Central Laboratory,The Seventh People's Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai200137,China)

机构地区：[1]上海中医药大学附属第七人民医院中心实验室,上海200137

出　　处：《上海中医药杂志》2023年第8期38-43,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81703791);上海市浦东新区卫健委优秀青年医学人才培养计划项目(PWRq2017-02)。

摘　　要：目的探讨金丝桃苷对高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)模型大鼠脂质代谢的影响及其作用机制。方法Wistar大鼠高脂饮食喂养6周,造模成功后随机分为模型对照组(n=10)、金丝桃苷低剂量组(50 mg·kg^(-1),n=10)和金丝桃苷高剂量组(100 mg·kg^(-1),n=10);另设空白对照组予正常饲料喂养(n=10)。各组均灌胃给药,每日1次。每周测量大鼠的体质量;干预6周后,检测大鼠肝功能和脂质代谢指标,苏木精-伊红(HE)染色法观察大鼠肝组织的病理形态改变,Western blot法检测大鼠肝组织脂质代谢相关蛋白的表达水平。结果与空白对照组比较,模型对照组大鼠肝脏有明显的脂肪变性。与模型对照组比较,金丝桃苷高剂量组大鼠肝内脂滴空泡、肝组织脂肪变性有明显改善,肝组织中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)水平显著降低(P<0.05),脂肪合成相关蛋白胆固醇调节元件结合蛋白1(SREBP1)、乙酰辅酶A羧化酶(ACC)、脂肪酸合酶(FASN)、硬脂酰辅酶A去饱和酶1(SCD1)表达量显著下调(P<0.05),脂肪分解相关蛋白过氧化物酶体增殖物激活受体α(PPARα)、肉毒碱棕榈酰基转移酶1A(CPT1A)表达量明显增加(P<0.05),且磷酸化腺苷酸活化蛋白激酶α(p-AMPKα)蛋白表达量升高(P<0.05),差异均有统计学意义。结论金丝桃苷可能通过调节腺苷酸活化蛋白激酶(AMPK)通路抑制肝脏脂质合成,促进脂质分解,说明金丝桃苷可能是治疗NAFLD的潜在药物。Objective To investigate the effect of hyperoside on lipid metabolism in a high-fat diet-induced non-alcoholic fatty liver disease(NAFLD)model rats and its mechanism of action.Methods Wistar rats were fed a high-fat diet for 6 weeks.After successful modeling,they were randomly divided into a high-fat diet(HFD)group(n=10),a hyperoside low-dose group[50 mg·kg^(-1)(LDG),n=10]and a hyperoside high-dose group[100 mg·kg^(-1)(HDG),n=10].A negative control(NC)group was set with rats being fed with normal chow(n=10).All groups were administered by gavage once a day.The weight of rats in each group was measured weekly.After 6 weeks of intervention,the liver function and lipid metabolism indexes of the rats were detected,the pathomorphological changes of rat liver tissues were observed with the hematoxylin-eosin(HE)staining,and the expression levels of lipid metabolism-related proteins in rat liver tissues were detected with Western blot method.Results There was significant steatosis in the liver of rats in the HFD group compared with the condition in the NC group.Compared with the condition in the HFD group,there was significant improvement in lipid droplet vacuoles and hepatic steatosis in rats with high doses of hyperoside;the levels of total cholesterol(TC),triacylglycerol(TG),and low-density lipoprotein(LDL)in liver tissues decreased significantly(P<0.05);the expression levels of lipid synthesis-related proteins including cholesterol regulatory element binding protein 1(SREBP1),acetyl coenzyme A carboxylase(ACC),fatty acid synthase(FASN),and stearoyl coenzyme A desaturase 1(SCD1)were downregulated significantly(P<0.05);the expression levels of lipolysis-related proteins including peroxisome proliferator-activated receptorα(PPARα),carnitine palmitoyltransferase 1A(CPT1A)increased significantly(P<0.05);and the expression level of phosphorylated adenylate-activated protein kinaseα(p-AMPKα)also observably increased(P<0.05).All the differences were statistically significant.Conclusion Hyperoside may inhibit hepatic li

关 键 词：非酒精性脂肪性肝病 金丝桃苷 腺苷酸活化蛋白激酶通路 脂质代谢 大鼠模型 中药研究 

分 类 号：R285.5[医药卫生—中药学]