Department of Cardiology, Affiliated Hospital of Jining Medical University, Jining, 272000, Shandong, People's Republic of China.
Department of Clinical Laboratory, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, 272000, Shandong, People's Republic of China.
Inflamm Res. 2019 Oct;68(10):867-876. doi: 10.1007/s00011-019-01268-2. Epub 2019 Jul 16.
A drastic reduction in myocardial cell apoptosis plays a crucial role in the treatment/management of myocardial infarction, a major cardiovascular health challenge confronting the world, especially the Western world. Accumulating evidence indicates that the cardiotoxicity caused by the apoptotic machinery is partly regulated by miRNAs. The aim of this research is to investigate the role of miR-138-5p on hypoxia/reperfusion-induced heart injury.
The expression of miR-138-5p was determined in heart tissue from myocardial infarction patients and rats. Rats were transfection with a miR-138-5p inhibitor to silence miR-138-5p. The cardiac function of rats was detected via echocardiography. SIRT1 and PGC-1α expression in cardiac infarction was detected via quantitative Real-time PCR (qPCR) and Western blot analysis, while the TUNEL assay was used to determine myocardial apoptosis.
Our observations showed that miR-138-5p expression was upregulated after the induction of myocardial infarction. The miR-138-5p inhibitor significantly improved cardiac function, increased the expression of SIRT1 and PGC-1α, and decreased the rate of myocardial apoptosis, whereas siRNA-SIRT1 reversed these protective effects.
In conclusion, our study demonstrated that miR-138-5p could promote cardiac ischemia injury via inhibition of the silent information regulator 1 and peroxisome proliferator-initiated receptor gamma and coactivator 1 alpha (SIRT1-PGC-1α) axis.
心肌细胞凋亡的急剧减少在治疗/管理心肌梗死中起着至关重要的作用，心肌梗死是全世界，尤其是西方世界面临的主要心血管健康挑战。越来越多的证据表明，凋亡机制引起的心脏毒性部分受 miRNAs 调节。本研究旨在探讨 miR-138-5p 在缺氧/再灌注诱导的心脏损伤中的作用。
检测心肌梗死患者和大鼠心脏组织中 miR-138-5p 的表达。用 miR-138-5p 抑制剂转染大鼠以沉默 miR-138-5p。通过超声心动图检测大鼠的心脏功能。通过定量实时 PCR(qPCR)和 Western blot 分析检测心肌梗死中 SIRT1 和 PGC-1α 的表达，同时通过 TUNEL 测定法检测心肌细胞凋亡。
我们的观察表明，心肌梗死后 miR-138-5p 的表达上调。miR-138-5p 抑制剂显著改善心脏功能，增加 SIRT1 和 PGC-1α 的表达，并降低心肌细胞凋亡率，而 siRNA-SIRT1 逆转了这些保护作用。
综上所述，本研究表明，miR-138-5p 可通过抑制沉默信息调节因子 1 和过氧化物酶体增殖物激活受体γ和共激活因子 1α(SIRT1-PGC-1α)轴促进心脏缺血损伤。
