绞股蓝总苷对PCSK9基因表达及辛伐他汀降血脂作用的影响

发布时间：2018-01-28 01:43

本文关键词： 绞股蓝总苷高脂血症 PCSK基因低密度脂蛋白受体辛伐他汀　出处：《中国病理生理杂志》2017年01期 　论文类型：期刊论文

【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(P0.05),各组HDLC水平有不同程度的上升(P0.05)。与model组大鼠比较,simvastatin组、GPs组以及combined组肝指数均明显下降(P0.05)。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(P0.05),GPs组LDLR的mRNA表达变化不明显,combined组LDLR的mRNA表达明显升高(P0.05)。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(P0.05)。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。
[Abstract]:Objective: to study the total glucosides of gynostemma pentaphyllum (Gypenosides). The effect of GPs on rat liver protein converting enzyme lysogenin 9 and PCSK9). Gene expression and the effect of simvastatin on lowering blood lipids. Methods: the hyperlipidemia model of rats was established by feeding with high fat diet. 60 healthy male SD rats were randomly divided into normal control group (n = 60). Control group. Hyperlipidemia model group and simvastatin group). GPs group and GPs combined with simvastatin group were fed with normal diet except normal control group. The other three groups of rats were fed with high fat diet. GPs was dissolved in 0.3% CMC-Na solution. The rats in the control and model groups were given 0.3CMC-NaA1ml / 100g by gavage). GPs group was administrated with GPs 160mg 路kg ~ (-1) 路d ~ (-1) and simvastatin group (n = 5 mg 路kg ~ (-1)) 路d ~ (-1)). The rats in the combined group were sacrificed after 8 weeks of the experiment. The blood samples were taken from the abdominal cavity to determine the serum total cholesterol (TC) and triglyceride (TG). High density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C); The weight and wet weight of liver tissue were measured and the liver index was measured. The liver was fixed with 4% paraformaldehyde and paraffin-embedded HE staining was used for routine morphological examination. The total RNAs were extracted from the liver to detect the mRNA expression of PCSK9 and LDLRs of low density lipoprotein receptor (LDLR). Results: the rat model of hyperlipidemia was successfully established and compared with that of model group. TG and LDL-C levels in simvastatin group and combined group were significantly decreased (P 0.05). The level of HDLC in each group increased to some extent (P 0.05). Compared with model group, simvastatin group was different from simvastatin group. The liver index of GPs group and combined group decreased significantly (P 0.05). The pathological results of liver tissue showed that fatty liver lesion appeared in hyperlipidemic rats. The degree of steatosis of hepatocytes in Simvastatin group and combined group was reduced in varying degrees. The expression of mRNA in simvastatin group was significantly higher than that in simvastatin group, especially in combined group. The expression of mRNA in simvastatin group was significantly higher than that in simvastatin group. The expression of mRNA in PCSK9 in GPs group and combined group was significantly lower than that in P0.05GPs group. There was no significant change in mRNA expression of LDLR in P0.05GPs group. The expression of LDLR mRNA in combined group was significantly higher than that in model group. The protein expression of PCSK9 and LDLR in Simvastatin group was significantly higher than that in control group. The expression of PCSK9 protein in GPs group and combined group was significantly decreased, and the expression of LDLR protein was significantly increased (P 0.05). Conclusion: 1. GPs can inhibit the expression of PCSK9 in liver. Increase the expression of LDLR; The combination of simvastatin and simvastatin can enhance the effect of lowering blood lipid and reducing hepatic fatty lesion.
【作者单位】：遵义医学院生物化学教研室;遵义医学院附属医院小儿内二科;
【基金】：贵州省科技厅基金资助项目(黔科合J字【2009】2-178号)
【分类号】：R285.5
【正文快照】： 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 o

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