【摘要】 目的探讨丹参酮ⅡA对于心力衰竭大鼠心肌凋亡的影响及调控miR-133水平的机制。方法采用胸主动脉缩窄法(TAC)建立心力衰竭大鼠模型,并给予连续12周的丹参酮ⅡA磺酸钠注射液治疗,同时部分心力衰竭大鼠皮下植入渗透泵持续泵入miR-133抑制剂antagomirs,以观察其抑制miR-133的水平。分析12周后的血流动力学情况、心肌细胞的凋亡情况(采用TUENL法)、心肌促凋亡基因(Bax和Caspase-3)以及抑制凋亡基因(Bcl-2)的表达情况(采用Western blot及RT-PCR法)。结果与假手术比较,TAC处理可导致心功能恶化(除平均动脉压外),心肌细胞的凋亡水平升高,Bax和Caspase-3蛋白和mRNA水平均上升,miR-133及Bcl-2蛋白和mRNA水平均下调;给予丹参酮ⅡA处理的TAC大鼠,除了心功能中的心率没有改善外,其余指标均有显著改善,且差异有统计学意义;皮下连续泵入antagomirs能够部分消除丹参酮ⅡA的作用。结论丹参酮ⅡA可降低心力衰竭大鼠的心肌凋亡水平,可能的机制是上调miR-133水平实现的。更多还原

【Abstract】 Objective To explore the effects of Tanshinone ⅡA(Tan ⅡA) on the myocardial apoptosis in rats with heart failure and its mechanisms for regulating the miR-133 levels.Methods The heart failure rat model was established by thoracic aorta constriction(TAC).Tan ⅡA Injection was applied for 12 successive weeks.Meanwhile,partial heart failure rats were subcutaneously implanted with osmotic pump of antagomirs to observe its inhibition on the miR-133 level.Twelve weeks later,the hemodynamic conditions,the myocardial apoptosis(using TUENL method),myocardial pro-apoptotic genes(Bax and Caspase-3),and the expressions of anti-apoptosis genes(Bcl-2)(using Western blot and RT-PCR method) were analyzed.Results Compared with the sham-operation group,TAC operation could deteriorate the heart function(except the mean arterial pressure),elevate the myocardial apoptosis level,increase the protein and mRNA levels of Bax and Caspase-3,and down-regulate the protein and mRNA levels of miR-133 and Bcl-2.TAC rats treated by Tan ⅡA could significantly improve all indices with statistical difference except the heart rate.Subcutaneously pumping of antagomirs could partially abolish the anti-apoptosis effect of Tan ⅡA.Conclusion Tan ⅡA could decrease the myocardial apoptosis level of heart failure rats,which was possibly realized by up-regulating the miR-133 level.更多还原