益气逐瘀方改善心肌梗死大鼠心肌损伤及对miR-24/Bim通路相关蛋白表达的影响

Effects of Yiqi Zhuyu Formula on Improving Cardiac Injury and miR-24/Bim Signal Pathway Related Protein Expression in Myocardial Infarction Rats

目的:探讨益气逐瘀方参元丹对急性心肌梗死大鼠心肌损伤及miR-24/Bim通路相关蛋白表达的影响。方法:50只SD大鼠随机分为假手术组、模型组、参元丹高、中、低剂量组,每组10只,采用左冠状动脉前降支结扎法复制心肌梗死模型,参元丹高、中、低剂量组从术后第2天开始给予参元丹药液灌胃,假手术组和模型组给予等剂量生理盐水灌胃,共给药2周。治疗结束后检测大鼠血清CK、LDH水平及心肌组织miR-24基因表达,超声心动图检测左室功能,Western-blot检测心肌组织Bim、Bcl-2、Bax、caspase-9蛋白表达。结果:实验结束时,与模型组比较,参元丹高、中、低剂量组均能显著降低血清CK、LDH水平(P<0.05,P<0.01),升高心肌组织miR-24基因表达(P<0.05,P<0.01),降低左室舒张和收缩末期内径(P<0.05,P<0.01),升高左室短轴缩短率及射血分数(P<0.05,P<0.01),升高心肌组织Bcl-2蛋白表达(P<0.05),降低Bim、Bax、caspase-9蛋白表达(P<0.05,P<0.01)。结论:益气逐瘀方参元丹可能通过调控miR-24/Bim信号通路相关细胞因子蛋白表达改善心肌梗死细胞损伤。

Objective： To investigate the effects of Yiqi Zhuyu formula Shenyuan Dan（ SYD） on myocardium injury biomarkers,cardiac function,miR-24/Bim pathway protein expression in myocardial infarction rats. Methods： Fifty SD rats were randomly divided into five groups namely sham group,model group,high-,middle-,and low-dose SYD group,with 10 rats in each group. The rat myocardium ischemia model was established by ligating of anterior descending branch of coronary artery. The rats in treatment groups were performed with intragastric administration of SYD for 2 weeks. After the treatment,serum levels of creatine kinases（ CK）,lactate dehydrogenase（ LDH）,and cardiac function were measured. miR-24 mRNA expression was measured by RT-PCR.Bim,Bcl-2,Bax and caspase-9 protein expression in ischemic myocardium were measured by Western-blot. Results： At the end of the treatment,the serum levels of CK,LDH were significantly decreased in SYD（ high,middle and low-dose） groups compared with those in model group（ P 〈0. 05,P 〈0. 01）. The cardiac function was also improved with the LVEDD and LVESD significantly decreased（ P 〈0. 05,P 〈0. 01）,and the LVFS and EF significantly increased（ P 〈0. 05,P 〈0. 01）. The expression of miR-24 mRNA and Bcl-2 protein in ischemic myocardium were significantly increased and the Bim,Bax,caspase-9 protein were significantly decreased in SYD groups compared with those in model group（ P 〈0. 05,P 〈0. 01）. Conclusion： Yiqi Zhuyu formula SYD could relieve myocardial injury and the possible mechanism may be related to adjusting miR-24/Bim signal pathway and its related protein expression in ischemic myocardium.