摘要
目的:探讨番连化浊方对急性高脂血症小鼠胆固醇代谢紊乱的调节作用.方法:采用Triton-WR1339构建C57BL/6小鼠急性高脂血症模型,给药5 d后,测定血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、谷草转氨酶(GOT)、谷丙转氨酶(GPT)含量;苏木精-伊红(HE)染色观察肝脏病理变化;油红O染色检测肝脏内脂质累积情况;蛋白质印迹法检测肝脏去唾液酸糖蛋白受体1(ASGR1)、肝X受体α(LXRα)、三磷酸腺苷结合盒转运蛋白A1(ABCA1)、ABCA5、细胞色素P450 7A1(CYP7A1)蛋白表达变化.结果:与模型组比较,番连化浊方能显著降低血清中TC、TG、LDL-C、GOT、GPT含量,同时升高HDL-C含量(均P<0.05);显著上调ABCA1、ABCG5、LXRα、CYP7A1蛋白表达水平,显著下调ASGR1蛋白表达水平(均P<0.05);显著减少肝细胞内脂质累积,改善肝脏病理形态.结论:番连化浊方可能通过调控ASGR1/LXRα/CYP7A1信号通路促进急性高脂血症小鼠的胆固醇外排,降低血脂.
Abstract
Objective:To investigate the regulatory effect of Fanlian Huazhuo Formula on cholesterol metabolism disorder in mice with acute hyperlipidemia.Methods:An acute hyperlipidemia model was established in C57BL/6 mice using Triton-WR1339.After 5 days of treatment,serum levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),glutamic oxalacetic transaminase(GOT),and glutamic-pyruvic transaminase(GPT)were measured.Hematoxylin-eosin(HE)staining was used to observe pathological changes in the liver.Oil Red O staining was per-formed to detect lipid accumulation in the liver.Western blot was used to detect changes in the expression of asialoglycoprotein re-ceptor 1(ASGR1),liver X receptor α(LXRα),ATP-binding cassette transporter A1(ABCA1),ABCA5,and cytochrome P450 7A1(CYP7A1)in the liver.Results:Compared with the model group,Fanlian Huazhuo Formula significantly reduced serum levels of TC,TG,LDL-C,GOT,and GPT,increased HDL-C levels(all P<0.05),significantly upregulated the protein expression levels of ABCA1,ABCG5,LXRα,and CYP7A1,significantly downregulated the protein expression level of ASGR1(all P<0.05),signifi-cantly reduced lipid accumulation in hepatocytes,and improved liver pathology.Conclusion:Fanlian Huazhuo Formula may pro-mote cholesterol efflux and reduce blood lipids in mice with acute hyperlipidemia by regulating the ASGR1/LXRα/CYP7A1 signa-ling pathway.
基金项目
国家自然科学基金青年科学基金项目(82305119)
广东省基础与应用基础研究基金项目(2022A1515011307)