复方四参颗粒对动脉粥样硬化豚鼠心肌损伤的保护作用

Protective Effects of Compound Sishen Granule on Myocardial Injury in Guinea Pigs with Atherosclerosis

目的:探讨复方四参颗粒对动脉粥样硬化引发心肌损伤的保护作用及其可能的作用机制。方法:将60只雄性豚鼠随机分为6组,分别为空白组、模型组、阳性药物(稳心颗粒)组及复方四参颗粒高、中、低剂量组,每组各10只。空白组给予标准饮食;其余各组复制动脉粥样硬化病理模型,并于第8周造模成功后,模型组给予0.9%Na Cl溶液灌胃,稳心颗粒组及复方四参颗粒各组按设定剂量灌胃给药。连续用药4周后,动脉采血并采集心脏,检测血清乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK);测算心脏指数,并检测心肌细胞凋亡情况及相关凋亡因子的表达。结果:模型组LDH、CK和心质量指数、心室指数均较空白组显著提高(P<0.01),而稳心颗粒组、复方四参颗粒高剂量组各指标均较模型组显著降低(P<0.01),中剂量组的LDH和CK值也显著降低(P<0.05)。模型组的心肌细胞凋亡率和坏死率均明显高于空白组(P<0.01),而稳心颗粒组、复方四参颗粒高剂量组均较模型组显著改善(P<0.01),复方四参颗粒中、低剂量在细胞凋亡中晚期也有明显改善(P<0.05);模型组Bcl-2蛋白表达较空白组明显下降、Bax与Fas蛋白表达均显著升高(P<0.01),稳心颗粒组与复方四参颗粒高剂量组与模型组比较均可显著提高Bcl-2表达、降低Bax与Fas表达(P<0.01),复方四参颗粒中剂量组可提高Bcl-2表达(P<0.01),中、低剂量组均可显著降低Fas表达(P<0.01)。结论:复方四参颗粒对动脉粥样硬化引起的心肌损伤有显著的保护作用,其作用机制可能与双向调节凋亡相关因子,从而抑制心肌细胞凋亡有关。

Objective: To discuss the protective effects of Compound Sishen Granule on myocardial injury induced by atherosclerosis and its possible mechanism. Methods: Sixty male guinea pigs were randomly divided into six groups,including blank group,model group,positive drug(Wenxin Granule) group,Compound Sishen Granule groups with low-,middle-and highdose,10 guinea pigs in each group. The blank group was given the standard diet,and the pathological model of atherosclerosis was replicated in the other groups. After 8 weeks in the successful modeling animals,the model group was treated with 0. 9%Na Cl solution for intragastric administration,and the Wenxin Granule group and Compound Sishen Granule groups with different doses were treated with the corresponding drug at the setting dose for intragastric administration. After drug intervention for continuous 4 weeks,the blood was collected from artery and the heart was collected. The serum levels of lactate dehydrogenase(LDH) and phosphocreatine kinase(CK) were detected,the cardiac index was calculated,and the apoptosis of cardiomyocytes and the expressions of related apoptosis factors were detected. Results: Compared with the blank group,the levels of LDH and CK and the cardiac index and ventricular index were all significantly increased in the model group(P < 0. 01),while these indicators were all significantly decreased in the Wenxin Granule group and Compound Sishen Granule group with high-dose(P < 0. 01),and the levels of LDH and CK were significantly decreased in the Compound Sishen Granule group with middledose compared with the model group(P < 0. 05). The apoptosis rate and necrosis rate of cardiomyocytes in the model group were significantly higher than those in the blank group(P < 0. 01),while the apoptosis rate and necrosis rate were significantly improved in the Wenxin Granule group and Compound Sishen Granule group with high-dose(P < 0. 01),and the apoptosis rate in middle and late stage was significantly decreased in the Compound Sishen Granule groups with middle-and low-dose compared with the model group(P < 0. 05). Compared with the blank group,the protein expression of Bcl-2 was obviously decreased and the protein expressions of Bax and Fas were significantly increased in the model group(P < 0. 01). Compared with the model group,the Bcl-2 expression was significantly increased and the Bax and Fas expressions were significantly decreased in the Wenxin Granule group and Compound Sishen Granule group with high-dose(P < 0. 01),and the Bcl-2expression was increased in the Compound Sishen Granule group with middle-dose(P < 0. 01),and the Fas expression was significantly decreased in the Compound Sishen Granule groups with middle-and low-dose(P < 0. 01). Conclusion:Compound Sishen Granule shows the significant protection on myocardial injury induced by atherosclerosis,its mechanism may be related to the bidirectional regulation of apoptosis related factors and the inhibition of cardiomyocyte apoptosis.