固醇调节因子结合蛋白-1在肝豆状核变性脂代谢中的作用及茵陈五苓散对其影响的研究  

Role of SREBP1 in lipid metabolism of hepatolenticular degeneration and effects of Yinchen Wuling Powder

作　　者：刘宇 朱宏[2] 李若梦[2] 谷绍娟[3] LIU Yu;ZHU Hong;LI Ruo-meng;GU Shao-juan(The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University,Chnagsha 410006,China;Traditional Chinese Medicine Department,The Third Xiangya Hospital of Central South University,Changsha 410013,China;Neurology Department,The Third Xiangya Hospital of Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅医学院附属肿瘤医院,长沙410006 [2]中南大学湘雅三医院中医科,长沙410013 [3]中南大学湘雅三医院神经内科,长沙410013

出　　处：《中华中医药杂志》2020年第1期346-349,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：湖南省自然科学基金青年基金项目(No.2018JJ3798)。

摘　　要：目的:研究固醇调节因子结合蛋白-1(SREBP1)在肝豆状核变性脂代谢中作用及茵陈五苓散对其调控机制。方法:采用ATP7B siRNA干扰HepG2细胞构建肝豆状核变性细胞模型;采用RT-PCR和Western Blot法检测对照干扰组、ATP7B干扰组24、48、72h细胞SREBP1基因表达和蛋白水平的变化情况;60只铜负荷小鼠随机分为正常对照组、高铜组、低剂量茵陈五苓散组和高剂量茵陈五苓散组,采用RT-PCR和Western Blot法检测各组SREBP1基因表达和蛋白水平的变化情况。结果:与对照干扰组比较,ATP7B siRNA干扰HepG2细胞24、48、72h后,ATP7B基因和蛋白的表达均明显下降,其中ATP7B siRNA干扰48h可达最大干扰效率(P<0.05,P<0.01)。ATP7B siRNA干扰组24、48、72h较正常对照组SREBP1 mRNA和蛋白表达均下调(P<0.05)。低、高剂量茵陈五苓散组铜负荷小鼠SREBP1 mRNA和蛋白表达均有上调(P<0.05)。结论:肝豆状核变性细胞模型中SREBP1表达下调,茵陈五苓散可上调SREBP1进而改善肝脏组织脂质代谢障碍。Objective:To investigate the role of SREBP1 in lipid metabolism of hepatolenticular degeneration and the regulation mechanism of Yinchen Wuling Powder.Methods:Using the method of ATP7B siRNA interference to interfere with HepG2 cells,and the hepatolenticular degeneration cell model is successfully constructed.The expression and protein level of SREBP1 in negative control siRNA interference group,ATP7B siRNA interference group at 24h,48h and 72h were detected by RT-PCR and Western Blot.Sixty copper load mice were randomly divided into group A:normal control group,B group:high copper group,C group:low dose Yinchen Wuling Powder group and D group:high dose Yinchen Wuling Powder group.The changes of SREBP1 gene expression and protein level in each group were measured by RT-PCR and Western Blot.Results:Compared to control cells,transfection of HepG2 cells with ATP7B siRNA resulted in decreased mRNA expression and decreased protein levels at 24h,48h and 72h respectively,and transfection with 5nM ATP7B siRNA for 48h up to a maximum interference efficiency (P<0.05,P<0.01).Compared with control group,the mRNA and protein expressions of SREBP1 were decreased in ATP7B siRNA interference group for 24h,48h and 72h respectively (P<0.05).In vivo experiments,SREBP1 mRNA and protein expression were increased in high and low dose Yinchen Wuling Powder group (P<0.05).Conclusion:The copper load is involved in lipid metabolism of hepatolenticular degeneration by down regulating the SREBP1 signal pathway,and the Yinchen Wuling Powder could activate SREBP1 and then improve the lipid metabolism disorder of liver tissue.

关 键 词：肝豆状核变性 茵陈五苓散 固醇调节因子结合蛋白-1 脂质代谢障碍 

分 类 号：R285.5[医药卫生—中药学]