microRNA-22 attenuates myocardial ischemia-reperfusion injury via an anti-inflammatory mechanism in rats.
microRNA-22 attenuates myocardial ischemia-reperfusion injury via an anti-inflammatory mechanism in rats.
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microRNA-22通过抗炎机制减轻大鼠心肌缺血再灌注损伤
DOI：
10.3892/etm.2016.3777
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发表时间：
2016-11
影响因子：
2.7
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Yang J;Fan Z;Yang J;Ding J;Yang C;Chen L
先前的研究报道了microRNA-22 （miR-22）可能与缺血再灌注（I/R）诱导的心肌损伤有关。我们之前发表的数据也表明，miR-22可能通过靶向cAMP反应元件结合蛋白结合蛋白（CBP），通过抗凋亡来保护大鼠心肌I/R损伤。然而，miR-22在心肌I/R损伤中的具体功能还远未完全阐明。本研究旨在探讨miR-22在心肌I/R损伤中的另一种心脏保护信号机制。选取成年雄性sd大鼠40只，随机分为4组（n=10）：假手术组、心肌I/R组、表达scramble miRNA的心肌I/R组（Ad-Scramble）和表达miR-22的心肌I/R组（Ad-miR-22）。除假手术组外，其余3组人工冠脉闭塞30 min，再灌注4 h，光镜下观察心肌结构变化；采用逆转录聚合酶链反应检测miR-22 mRNA表达水平；采用Evans Blue/三苯四唑氯双染色法分析心肌梗死面积；western blot检测p38丝裂原活化蛋白激酶（MAPK）、CBP、c-Jun-activator protein (AP)-1和phospho (p)-c-Jun-AP-1表达蛋白水平。ELISA法检测大鼠心肌组织中TNF-α、IL-6水平。结果表明，腺病毒介导的miR-22过表达显著降低p38 MAPK、CBP、c-Jun-AP-1、p-c-Jun-AP-1的表达水平，并伴有心肌损伤的改善，包括梗死面积缩小，肌酸激酶、乳酸脱氢酶和促炎症介质（肿瘤坏死因子-α和白细胞介素-6）的释放减少。这些发现提示miR-22对心肌I/R损伤具有保护作用。这种保护机制，至少部分是由于其通过抑制p38 MAPK/CBP/c-Jun-AP-1信号通路的抗炎功能。
Previous studies have reported that microRNA-22 (miR-22) may be implicated in ischemia-reperfusion (I/R)-induced myocardial injury. Our previously published data also demonstrated that miR-22 may protect against myocardial I/R injury via anti-apoptosis in rats by targeting cAMP response element-binding protein binding protein (CBP). However, the specific function of miR-22 in myocardial I/R injury is far from fully elucidated. The present study was designed to investigate another cardioprotective signaling mechanism of miR-22 in myocardial I/R injury. A total of 40 adult male Sprague-Dawley rats were randomly divided into four equal groups (n=10): Sham, myocardial I/R, myocardial I/R with adenovirus expressing scramble miRNA (Ad-Scramble) and myocardial I/R with adenovirus expressing miR-22 (Ad-miR-22) groups. Besides the Sham operation group, the remaining three groups were artificially afflicted with coronary occlusion for 30 min and subsequently reperfused for 4 h. A light microscope was used to observe structural changes in the myocardium; reverse transcription polymerase chain reaction was used to measure the miR-22 mRNA expression level; the myocardial infarct size was analyzed by the Evans Blue/triphenyltetrazolium chloride double-staining; and p38 mitogen-activated protein kinase (MAPK), CBP, c-Jun-activator protein (AP)-1 and phospho (p)-c-Jun-AP-1 expression protein levels were detected by a western blot. Furthermore, ELISA was used to measure the levels of TNF-α and IL-6 in the myocardium. The results demonstrated that adenovirus-mediated miR-22 overexpression markedly reduced p38 MAPK, CBP, c-Jun-AP-1, p-c-Jun-AP-1 expression levels concomitant with an improvement in myocardial injury, including smaller infarct size, reduced release of creatine kinase, lactate dehydrogenase and proinflammation mediators (tumor necrosis factor-α and interleukin-6). These findings suggest that miR-22 has a protective effect on myocardial I/R injury. This protection mechanism, at least in part, is due to its anti-inflammatory function via the suppression of the p38 MAPK/CBP/c-Jun-AP-1 signaling pathway.
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影响因子：
64.5
作者：
Avantaggiati, ML;Ogryzko, V;Kelly, K
通讯作者：
Kelly, K
影响因子：
3.8
作者：
Hu, Huilin;Zhai, Changlin;Tang, Guanmin
通讯作者：
Tang, Guanmin
影响因子：
3.8
作者：
Doddakula, Kishore K.;Neary, Peter M.;Redmond, Henry P.
通讯作者：
Redmond, Henry P.
缺血和再灌注 - 从翻译机构。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3
作者：
Surinkaew, Sirirat;Kumphune, Sarawut;Chattipakorn, Nipon
通讯作者：
Chattipakorn, Nipon