芪蛭通脉颗粒对冠心病血脂异常大鼠PCSK9/LDLR通路的影响

Effect of Qizhi Tongmai Granules on Dyslipidemia in Rats with Coronary Heart Disease Based on PCSK9/LDLR Pathway

目的观察芪蛭通脉颗粒对冠心病大鼠血脂异常的调节作用及对肝脏枯草溶菌素转化酶9(PCSK9)/低密度脂蛋白受体(LDLR)、血管细胞黏附分子-1(VCAM-1)/细胞间黏附分子-1(ICAM-1)通路的影响,探讨芪蛭通脉颗粒对冠心病大鼠血脂异常的可能作用机制。方法将60只Wistar大鼠随机分为空白对照组、冠心病模型组、阿托伐他汀组和芪蛭通脉颗粒高、中、低剂量组各10只。造模成功后,各治疗组分别给予阿托伐他汀和高、中、低剂量芪蛭通脉颗粒,连续治疗4周。治疗结束后,检测血清三酰甘油(TAG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),Westernblotting法检测PCSK9、LDLR、VCAM-1和ICAM-1蛋白水平。结果芪蛭通脉颗粒低、中、高剂量组大鼠血清TC、TAG、LDL-C水平较模型组均降低,HDL-C水平均较模型组升高,差异有统计学意义(P<0.05);与模型组比较,芪蛭通脉颗粒低、中、高剂量组PCSK9水平下调,LDLR水平上调,差异有统计学意义(P<0.05);与模型组比较,芪蛭通脉中、高剂量组VCAM-1和ICAM-1水平下调,差异有统计学意义(P<0.05)。结论芪蛭通脉颗粒低、中、高剂量组能够降低大鼠血清TC、TAG、LDL-C水平,提高HDL-C水平,其调脂作用可能是通过调控PCSK9/LDLR、VCAM-1/ICAM-1信号通路相关蛋白表达实现的。

Objective:To observe the regulating effect of Qizhi Tongmai Granules on dyslipidemia in rats with coronary heart disease and its influence on PCSK9/LDLR and VCAM-1/ICAM-1 pathways,and to explore the possible mechanism of Qizhi Tongmai Granules on dyslipidemia in rats with coronary heart disease.Methods:60 Wistar rats were randomly divided into the blank control group,coronary heart disease model group,atorvastatin group and Qizhi Tongmai Granules high,medium and low dose groups(n=10 in each group).After the model was successfully established,the treatment group was given atorvastatin as well as high,medium,and low dose of Qizhi Tongmai Granules for 4 consecutive weeks.After the experiment,the serum TAG,TC,HDL-C,LDL-C were detected,and the liver protein levels such as PCSK9,LDLR,VCAM-1 and ICAM-1 were detected by Western blotting.Results:The serum TC,TAG and LDL-C levels of rats in the Qizhi Tongmai Granules low,medium and high dose groups were lower than the model group,and the HDL-C levels were higher than the model group.The difference was statistically significant(P<0.05)Compared with the model group,the PCSK9 level of Qizhi Tongmai Granules low,medium and high dose groups was down-regulated,and the LDLR level was up-regulated,the difference was statistically significant(P<0.05),compared with the model group,the levels of VCAM-1 and ICAM-1 in the Qizhi Tongmai Granules medium and high dose group were down-regulated,and the difference was statistically significant(P<0.05).Conclusion:Qizhi Tongmai Granules low,medium and high dose groups can reduce the serum TC,TAG,LDL-C levels and increase HDL-C levels in rats.Its lipid-regulating effect may be achieved by regulating the expression of related proteins in the PCSK9/LDLR and VCAM-1/ICAM-1 signaling pathways.