microRNA-133a在心肌梗死后心力衰竭大鼠心肌细胞中的表达及抗凋亡作用
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The Anti-apoptosis Effect and Expression of microRNA-133a in Rat Myocardium of Heart Failure After Myocardial Infarction
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    摘要:

    目的 观察microRNA-133a(miR-133a)在心肌梗死后心衰大鼠心肌细胞中的表达及对细胞凋亡的影响。方法 SD大鼠随机分为四组:①假手术组:仅开胸不结扎冠状动脉;②心肌梗死组:结扎冠状动脉前降支;③rAAV9组:先冠状动脉转染空白病毒rAAV9后再结扎冠状动脉前降支;④miR-133a组:先冠状动脉转染rAAV9-ZsGreen-pre-miR-133a后再结扎冠状动脉前降支。饲养8周后,real-time PCR检测大鼠心肌miR-133a、Transgelin-2(TAGLN2)、Caspase-9、Bcl-2 mRNA水平,免疫组织化学和Western blot检测TAGLN2、Caspase-9、Bcl-2蛋白水平。结果 心肌梗死后心衰大鼠心肌组织中miR-133a的表达较假手术组相比显著下降(2.963±0.461比12.518±2.21),TAGLN2和Caspase-9的mRNA及蛋白表达升高,Bcl-2 mRNA和蛋白表达水平降低。冠状动脉注射rAAV9-ZsGreen-pre-miR-133a使大鼠心肌miR-133a表达明显上调,TAGLN2和Caspase-9的mRNA及蛋白表达减少,Bcl-2的mRNA和蛋白表达水平增加。结论 心肌梗死后心衰大鼠心肌miR-133a表达下调,可能使其对促凋亡基因TAGLN2和Caspase-9的降解和抑制作用减弱,从而促进心肌凋亡的发生;过表达miR-133a可能减少心肌梗死后的心肌凋亡。

    Abstract:

    Aim To observe the anti-apoptosis effect and expression of microRNA-133a (miR-133a) in rat myocardium of heart failure after myocardial infarction (MI). Methods Sprague-Dawley rats were divided into four groups randomly: ①Sham group: rats were dealt with open-chest ②MI group: rats were operated by left anterior descending coronary artery ligation ③rAAV9 group: rats were operated by left anterior descending coronary artery ligation after transfected with rAAV9-ZsGreen by coronary injection ④miR-133a group: rats were operated by left anterior descending coronary artery ligation after transfected with rAAV9-ZsGreen-pre-miR-133a by coronary injection.Feeding for eight weeks,expressions of miR-133a and mRNA of transgelin-2 (TAGLN2),Caspase-9 and Bcl-2 were detect by real-time PCR,immunohistochemistry and Western blot were used to determine protein level of TAGLN2,Caspase-9 and Bcl-2. Results The miR-133a expression of MI group decreased obviously compared with sham group (2.963±0.461 vs.12.518±2.21).The mRNA and protein level of TAGLN2 and Caspase-9 both increased in MI group versus sham group,while Bcl-2 expression decreased in MI group.The expression of miR-133a was up-regulated after rAAV9-ZsGreen-pre-miR-133a coronary injection,the mRNA and protein level of TAGLN2 and Caspase-9 were reduced in the same group,while Bcl-2 expression increased. Conclusions The down-regulation of miR-133a in failure heart after MI could decrease its degradation and inhibiting effects to TAGLN2 and Caspase-9,thus promote myocardial apoptosis.Myocardial apoptosis may be alleviated by over-expressed miR-133a.

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李安莹,杨 侃,杨 琼. microRNA-133a在心肌梗死后心力衰竭大鼠心肌细胞中的表达及抗凋亡作用[J].中国动脉硬化杂志,2014,22(10):1001~1008.

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  • 收稿日期:2014-01-10
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