Suppression of miR-34a Expression in the Myocardium Protects Against Ischemia-Reperfusion Injury Through SIRT1 Protective Pathway
Suppression of miR-34a Expression in the Myocardium Protects Against Ischemia-Reperfusion Injury Through SIRT1 Protective Pathway
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DOI：
10.1089/scd.2017.0062
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发表时间：
2017-09-01
影响因子：
4
通讯作者：
Tian, Hai
中科院分区：
文献类型：
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作者：
Fu, Bi-Cheng;Lang, Ji-Lu;Tian, Hai
MicroRNA-34 a（miR-34 a）在心肌中表达，并且在心肌损伤后表达改变。我们研究了miR-34 a对缺血再灌注（IR）损伤后心脏功能的影响。从新生大鼠心脏分离心肌细胞，并在体外诱导模拟IR损伤。在大鼠IR损伤后，使用超声心动图测量梗死面积并评价左心室（LV）功能。分析沉默信息调节因子1（SIRT 1）、乙酰化p53（ac-p53）、Bcl-2和Bax的蛋白表达以及miR-34 a和SIRT 1基因水平。miR-34 a过表达通过增加细胞凋亡和梗死面积以及降低LV功能来加剧心肌损伤。抑制miR-34 a可减轻心肌IR损伤。miR-34 a对SIRT 1的表达有负调控作用，其下游基因ac-p53、Bcl-2和Bax的表达也相应改变。miR-34 a的表达增加可加重IR后的损伤; miR-34 a抑制治疗可能代表心肌IR损伤的一种新的治疗方法。
MicroRNA-34a (miR-34a) is expressed in the myocardium and expression is altered after myocardial injury. We investigated the effects of miR-34a on heart function after ischemia-reperfusion (IR) injury. Cardiomyocytes were isolated from neonatal rat hearts and simulated IR injury was induced in vitro. Following IR injury in rats, infarct size was measured and left ventricular (LV) function was evaluated using echocardiography. Protein expression of silent information regulator 1 (SIRT1), acetylated p53 (ac-p53), Bcl-2 and Bax, and miR-34a and SIRT1 gene levels were analyzed. miR-34a overexpression exacerbated myocardial injury by increasing apoptosis and infarct size and decreasing LV function. Suppression of miR-34a attenuated myocardial IR injury. SIRT1 was negatively regulated by miR-34a and the expression of downstream genes, such as ac-p53, Bcl-2, and Bax were altered correspondingly. Increased expression of miR-34a aggravates injury after IR; miR-34a suppression therapy may represent a new line of treatment for myocardial IR injury.