丹参酮ⅡA对心力衰竭大鼠的心肌凋亡及miR-133水平的影响  

Effects of Tanshinone Ⅱ A on the Myocardial Apoptosis and the miR-133 Levels in Rats with Heart Failure

作　　者：冯俊[1] 李树生[1] 梁黔生[1] 屠恩远[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院急诊科,武汉430030

出　　处：《中国中西医结合杂志》2012年第7期930-933,共4页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.30500657)

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。Objective To explore the effects of Tanshinone IIA （Tan II A） 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 ]I A 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 ap- optosis （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 pres- sure）, 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 II A could significant- ly improve all indices with statistical difference except the heart rate. Subcutaneously pumping of antagomirs could partially abolish the anti-apoptosis effect of Tan II A. Conclusion Tan I1A could decrease the myocardial apoptosis level of heart failure rats, which was possibly realized by up-regulating the miR-133 level.

关 键 词：丹参酮ⅡA miR-133 心力衰竭大鼠 心肌凋亡 

分 类 号：R285.5[医药卫生—中药学]