Di Yun-Feng, Li De-Cai, Shen Yan-Qing, Wang Chun-Lei, Zhang Da-Yong, Shang An-Quan, Hu Teng
Department of Cardiology, Sichuan Mianyang 404 Hospital (The Second Affiliated Hospital of North Sichuan Medical College) No.56, Fucheng District, Mianyang City 621000, Sichuan Province, China.
Department of Cardiology, Wuxi Ho.2 People's Hospital, The Affiliated Hospital of Nanjing Medical University Wuxi, Jiangsu 214002, China.
Am J Transl Res. 2017 Feb 15;9(2):656-663. eCollection 2017.
MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, have been implicated as critical regulatory molecules in many cardiovascular diseases, including ischemia-/reperfusion-induced cardiac injury. In the present study, we report on the role of miR-146b in myocardial I/R injury and the underlying cardio-protective mechanism. Antagomir-146b was used to explore the effects of miR-146b on cardiac ischemia/reperfusion injury (30 min ischemia followed by 180 min reperfusion). As predicted, miR-146b overexpression significantly reduced the infarct size and cardiomyocytes apoptosis and release of creatine kinase and lactate dehydrogenase. In addition, miR-146b attenuated H9c2 cell apoptosis. Furthermore, Smad4 was predicted and verified as a potential miR-146b target using bioinformatics and luciferase assay. In summary, this study demonstrated that miR-146b plays a critical protective role in cardiac ischemic injury and may provide a new therapeutic approach for the treatment of myocardial I/R injury.
微小RNA是一类小的非编码RNA,可在转录或转录后调节其靶基因的表达,在包括缺血/再灌注诱导的心脏损伤在内的许多心血管疾病中,已被认为是关键的调节分子。在本研究中,我们报告了miR-146b在心肌缺血/再灌注损伤中的作用及潜在的心脏保护机制。使用抗miR-146b来探究miR-146b对心脏缺血/再灌注损伤(30分钟缺血后再灌注180分钟)的影响。正如预期的那样,miR-146b过表达显著减小了梗死面积,减少了心肌细胞凋亡以及肌酸激酶和乳酸脱氢酶的释放。此外,miR-146b减轻了H9c2细胞凋亡。此外,使用生物信息学和荧光素酶测定法预测并验证了Smad4是miR-146b的潜在靶标。总之,本研究表明miR-146b在心脏缺血性损伤中起关键保护作用,并可能为治疗心肌缺血/再灌注损伤提供一种新的治疗方法。