绞股蓝总苷对PCSK9基因表达及辛伐他汀降血脂作用的影响  

Effects of gypenosides on PCSK9 gene expression and blood lipids lowered by simvastatin

作　　者：吴柳松[1,2] 钱民章[1] 

机构地区：[1]遵义医学院生物化学教研室,贵州遵义563004 [2]遵义医学院附属医院小儿内二科,贵州遵义563004

出　　处：《中国病理生理杂志》2017年第1期79-85,共7页Chinese Journal of Pathophysiology

基　　金：贵州省科技厅基金资助项目(黔科合J字【2009】2-178号)

摘　　要：目的:探讨绞股蓝总苷(gypenosides,GPs)对大鼠肝脏前蛋白转化酶枯草溶菌素9(PCSK9)基因表达及辛伐他汀的降血脂作用的影响。方法:采用高脂饲料喂饲建立大鼠高脂血症模型。60只健康雄性SD大鼠随机分为正常对照组(control组)、高脂模型组(model组)、辛伐他汀组(Simvastatin组)、GPs组和GPs与辛伐他汀联合用药组(combined组)。除正常对照组喂食普通饲料外,其余3组大鼠均喂食高脂饲料。将GPs溶于0.3%羧甲基纤维素钠(CMC-Na)溶液中,用灌胃方式给药。Control组和model组灌0.3%CMC-Na(1mL/100 g),GPs组灌GPs 160 mg·kg^(-1)·d^(-1),simvastatin组灌辛伐他汀5mg·kg^(-1)·d^(-1),combined组灌两者联合剂量。实验8周后,处死大鼠。取腹腔动脉血,测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C);称大鼠体重及肝脏组织湿重,测定肝指数;取肝脏用4%多聚甲醛固定,石蜡包埋,HE染色作常规形态学检测;另取肝脏提取总RNA,real-time PCR测定PCSK9和低密度脂蛋白受体(LDLR)的mRNA表达;提取肝脏总蛋白,Western blot测定PCSK9和LDLR蛋白的表达。结果:成功建立高脂血症大鼠模型。与model组大鼠比较,simvastatin组、GPs组以及combined组TC、TG和LDL-C水平均明显下降(P<0.05),各组HDLC水平有不同程度的上升(P<0.05)。与model组大鼠比较,simvastatin组、GPs组以及combined组肝指数均明显下降(P<0.05)。肝组织病理结果显示,高脂血症性大鼠出现脂肪肝病变;Simvastatin组、GPs组以及combined组大鼠肝细胞脂肪变性程度有不同程度减轻,尤以combined组效果显著。与model组比较,simvastatin组PCSK9和LDLR的mRNA表达均明显升高,GPs组以及combined组PCSK9的mRNA表达明显降低(P<0.05),GPs组LDLR的mRNA表达变化不明显,combined组LDLR的mRNA表达明显升高(P<0.05)。与model组比较,Simvastatin组PCSK9和LDLR的蛋白表达均明显升高;GPs组和combined组的PCSK9蛋白表达�AIM：To explore the effect of gypenosides（GPs） on PCSK9 gene expression in hyperlipidemic rat liver and the blood lipids lowered by simvastatin.METHODS：Healthy male SD rats（n = 60） were randomized into 5groups：normal control group,hyperlipidemic model group,simvastatin group,GPs group and GPs combined with simvastatin group（combined group）.The rats in all groups were fed high-fat diet except normal control group which were fed with ordinary diet.The rats in control group and hyperlipidemic model group were gavaged with 0.3%CMC-Na every day.The rats in GPs group were gavaged with GPs at 160 mg·kg-1·d-1.The rats in simvastatin group were gavaged with simvastatin at 5 mg·kg-1·d-1.The rats in combined group were gavaged with GPs and simvastatin.The experiment lasted for8 weeks.The rats were anesthetized with chloral hydrate,and abdominal arterial blood samples were collected to detect the total cholesterol（TC）,triglyceride（TG）,low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C）.The body weight and the wet weight of the livers were measured,and the liver index was calculated.The pathological changes of the livers were observed under microscope with HE staining.The expression of PCSK9 and lowdensity lipoprotein receptor（LDLR） at mRNA and protein levels was determined by real-time PCR and Western blot.RESULTS：The model of hyperlipidemia rats was established successfully.Compared with model group,the levels of TC,TG and LDL-C in simvastatin group,GPs group and combined group were obviously decreased（P 〈0.05）,and the HDL-C levels were obviously upregulated（P 〈 0.05）.Compared with model group,the liver indexes in simvastatin group,GPs group and combined group were obviously decreased（P 〈0.05）.The pathological changes of the liver tissues showed that hepatic adipose appeared in model group,and that in simvastatin group and GPs group had different degrees of relief,especially in combined group.Compared with model group,the mRN

关 键 词：绞股蓝总苷 高脂血症 PCSK9基因 低密度脂蛋白受体 辛伐他汀 

分 类 号：R543.5[医药卫生—心血管疾病]