【摘要】 目的:探讨曲美他嗪(TMZ)与帕瑞昔布(parecoxib)联合给药对急性心肌梗死模型大鼠心脏的保护作用及其机制。方法:66只雄性SD大鼠随机分为假手术组(sham)、急性心肌梗死模型组(AMI)、曲美他嗪治疗组(AMI+TMZ)、帕瑞昔布钠治疗组(AMI+parecoxib)和曲美他嗪与帕瑞昔布钠联合治疗组(AMI+TMZ+parecox-ib)。大鼠实施冠状动脉左前降支结扎后,第3 d开始给药,第8 d检测大鼠心功能(HR、LVSP、LVEDP、+dp/dtmax和-dp/dtmax),测定心脏梗死面积,bax和bcl-2基因表达,COX-2、Bax、Bcl-2和cleaved caspase-3的蛋白表达,caspase-3活化以及心肌梗死周边区细胞凋亡率。结果:与假手术组相比,AMI模型组大鼠心肌梗死周边区COX-2蛋白表达明显增高(P<0.01);帕瑞昔布钠治疗组与AMI模型组相比,COX-2表达下降(P<0.01);联合给药治疗组与模型组相比,能显著改善心肌梗死大鼠的心脏收缩功能(LVSP与+dp/dtmax)(P<0.05),并使心肌梗死面积缩小(P<0.05),心肌梗死周边区细胞的凋亡率下降,并且治疗效果优于单独给药。联合给药治疗组与模型组相比,Bax/Bcl-2 mRNA和蛋白表达比例显著降低(P<0.05),caspase-3活性和cleaved caspase-3蛋白表达下降(P<0.05)。结论:帕瑞昔布钠与曲美他嗪联合给药治疗具有一定的协同保护缺血心肌的作用,其机制可能与共同抑制心肌细胞凋亡有关。更多还原

【Abstract】 AIM: To investigate the protective effects and mechanisms of combinational use of trimetazidine(TMZ) and parecoxib sodium on acute myocardial infarction(AMI) in rats.METHODS: Sixty-six Sprague-Dawley rats were randomly divided into 5 groups: sham group;AMI group;AMI+TMZ group;AMI+parecoxib group;AMI+TMZ+parecoxib group.All rats were sacrificed and cardiac functions(HR,LVSP,LVEDP,+dp/dtmax,-dp/dtmax) were measured with a Pclab-3804 biological signal processing system on the 8th day.The infarct size in each group was checked up by TTC staining method.RT-PCR was employed to detect the bax mRNA and bcl-2 mRNA.The protein levels of COX-2,Bax,Bcl-2 and cleaved caspase-3 in myocardium were determined by Western blotting.The activity of caspase-3 in each group was measured by colorimetric assay kit,and the apoptotic rates were detected with DNA ladder kit.RESULTS: Compared with sham group,increased expression of COX-2 protein(P<0.01) was observed in AMI group.The expression of COX-2 protein in parecoxib group was lower than that in AMI group(P<0.01).Compared with AMI group,the combinational use of trimetazidin and parecoxib improved contractile functions(LVSP and +dp/dtmax),reduced the infarct size and lowered the apoptotic rates remarkably.Specifically,the combinational use of trimetazidin and parecoxib showed better effects than use of trimetazidin or parecoxib alone.Reduced expression of Bax/Bcl-2 mRNA and protein,the reduced caspase-3 activity and cleaved caspase-3 expression were also found in combinational group as compared with other groups(P<0.05).CONCLUSION: The combinational use of trimetazidin and parecoxib effectively improves cardiac functions and reduces infarct size.The mechanism of the protective effect is probably associated with inhibiting apoptosis of cardiac myocytes.更多还原