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 5 groups:normal control group , hyperlipidemic model group , simvastatin group , GPs group and GPs combined with simvasta-tin 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 simvas-tatin at 5 mg・ kg-1・ d-1 .The rats in combined group were gavaged with GPs and simvastatin .The experiment lasted for 8 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 cho-lesterol ( 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 low-density lipoprotein receptor ( LDLR) at mRNA and protein levels was determined by real-time PCR and Western blot .RE-SULTS: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 , espe-cially in combined group .Compared with model group , the mRNA expression levels of PCSK 9 and LDLR in simvastatin group were obviously increased , while the mRNA expression levels of PCSK 9 in GPs group and combined group were obvi-ously decreased (P<0.05), and the mRNA expression of LDLR in combined group was obviously increased (P<0.05). Compared with model group , the protein expression of PCSK 9 and LDLR in simvastatin group was obviously increased , while the protein expression levels of PCSK 9 in GPs group and combined group were obviously reduced , and the LDLR pro-tein levels were obviously increased (P<0.05).CONCLUSION:Gypenosides inhibit the expression of PCSK9 and in-crease the expression of LDLR in the liver .The combination of gypenosides and simvastatin promotes the lipid-lowering effect of simvastatin and attenuates hepatic steatosis , which may be related to inhibiting the expression of PCSK 9 in the liv-er.%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（1 mL／100 g），GPs组灌GPs 160 mg・ kg－1・ d－1，simvastatin组灌辛伐他汀5 mg・ 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蛋白表达明显降低，LDLR蛋白表达明显升高（ P＜0．05）。结论：GPs能抑制肝脏PCSK9表达，增加LDLR表达量；与辛伐他汀联用可增强其降血脂和减轻肝脏脂肪病变的效果。
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