三七皂苷R1抑制ApoE基因敲除小鼠肝脏脂质沉积的作用及其机制研究  

Inhibiting effects and mechanisms of notoginsenoside R1 on liver lipid deposition in ApoE knocked out mice

作　　者：熊敏琪[1] 陈瑜[1] 张腾[1] XIONG Minqi;CHEN Yu;ZHANG Teng(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicin;Clinical Institute of Integrated Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai 200437, China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院上海市中医药研究院中西医结合临床研究所,上海200437

出　　处：《上海中医药杂志》2018年第5期65-70,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：上海市东方学者跟踪计划项目(GZ2015011);上海市优秀学术带头人项目(14XD1403500);上海市高校特聘教授(东方学者)人才计划项目[沪教委人(2010)84号;沪教委人(2011)88号];上海市085一流学科建设科技创新支持计划项目(085ZY1212;085ZY1221);上海市曙光计划项目(13SG42);国家中医药管理局中西医结合临床重点学科建设项目(国中医药发[2009]30号);国家自然基金面上项目(81273960)

摘　　要：目的探索三七皂苷R1抑制ApoE基因敲除小鼠肝脏脂质沉积的作用及其相关机制。方法将C57BL/6J小鼠作为正常组,将ApoE基因敲除小鼠随机分为模型组和三七皂苷R1组(25μg/g)。正常组及模型组接受溶剂治疗。腹腔注射8周进行干预。通过HE染色和油红O染色观察肝脏病理形态学及脂质沉积相关改变。提取肝脏组织总RNA,采用Real-time PCR分析肝脏PPARγ、LXRα、ABCA1和SRBI基因的表达以及miR-26a、miR-33和miR-122表达。结果肝脏HE染色和油红O染色结果显示:与正常对照组比较,模型组小鼠肝组织出现大量空泡样变,变性的肝细胞肿胀,肝细胞内见大量脂肪空泡和脂质沉积。与模型组比较,三七皂苷R1能显著减轻肝细胞肿胀,减少脂肪空泡和脂质沉积。肝脏脂质代谢相关基因和miRNA表达分析结果提示:与模型组比较,三七皂苷R1可显著上调肝脏PPARγ、LXRα、ABCA1以及SRBI的表达水平(P<0.05,P<0.01),显著下调肝脏miR-26a的表达水平(P<0.05)。结论三七皂苷R1可显著抑制ApoE基因敲除小鼠肝脏脂质沉积,其机制可能与调节胆固醇代谢作用相关。Objective To explore the inhibiting effects and mechanisms of notoginsenoside R1 on liver lipid deposition in ApoE knocked out（ ApoE^（-/-）） mice.Methods The wild type C57 BL/6 J mice were taken as the normal group. The ApoE^（-/-） mice were randomly divided into the model group and notoginsenoside R1 group. The normal group and the model group were treated with the solvent therapy,and the notoginsenoside R1 group was treated with notoginsenoside R1 at dose of 25 μg/g by intraperitoneal injection,with a course of 8 weeks. The changes on the liver pathological morphology and lipid deposition were observed after hematoxylin and eosin（ HE） staining and oil red O staining. The total RNA was extracted from the liver. The gene expressions of PPARγ,LXRα,ABCA1,SRBI and the expressions of miR-26 a,miR-33 and miR-122 were analyzed by Real-time PCR. Results The results of HE staining and oil red O staining revealed that compared with the normal control group,large vacuolation and degenerative hepatocytes swelling were observed in the liver tissues of mice in the model group,as well as a great number of lipid vacuoles and lipid deposition. Compared with the model group,the hepatocytes swelling was significantly relieved and the lipid vacuoles and lipid deposition were reduced in the notoginsenoside R1 group. The results of expression analysis on lipid metabolism-related genes and miRNAs revealed that compared with the model group, the expression levels of PPARγ,LXRα,ABCA1 and SRBI were significantly up-regulated in the notoginsenoside R1 group（ P〈0. 05,P〈0.01）,and the expression level of miR-26 a was significantly down-regulated（ P〈0.05）. Conclusion Notoginsenoside R1 can significantly suppress the liver lipid deposition in ApoE^（-/-） mice,and its mechanisms may be associated with regulation on cholesterol metabolism.

关 键 词：三七皂苷R1 肝脏 胆固醇代谢 

分 类 号：R285.5[医药卫生—中药学]