Pan Jialin, Zhou Lili, Lin Cong, Xue Weihao, Chen Peng, Lin Jiafeng
Division of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Division of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Evid Based Complement Alternat Med. 2022 Feb 28;2022:1388415. doi: 10.1155/2022/1388415. eCollection 2022.
Myocardial apoptosis occurs during myocardial ischemia. This study aimed to determine the effect of microRNA-34a (miR-34a) in ischemia-induced myocardial apoptosis. Mainly, SD rats were subjected to myocardial ischemia by ligaturing the left anterior descending branch of coronary artery. After rats had myocardial infarction, HE staining and TUNEL staining confirmed a significant increase in apoptosis. The expression of miR-34a was noticeably upregulated, while the expression of Notch1 was downregulated. An increase in caspase-3 and a decrease in Bcl-2/Bax ratio were observed in myocardium. Similar results were observed in the model of cardiomyocyte ischemia and anoxia of this study. When rat cardiomyocytes were administered with serum starvation and microaerophilic system, apoptosis-related proteins were significantly increased. However, transfecting the miR-34a inhibitor into the cardiomyocyte before the serum starvation and hypoxia treatment could increase the ratio of Bcl-2/Bax and downregulate the expression of caspase-3, as well as prevent cardiomyocytes from apoptosis. As opposed to the abovementioned points, the upregulation of miR-34a expression by transfecting miR-34a mimics induced Notch1 reduce and apoptosis-related proteins increase apparently, while upregulation of Notch1 could stimulate apoptosis attributed to miR-34a. Mechanistically, we demonstrated that Notch1 is a direct target of miR-34a. In conclusion, our current results suggested that miR-34a significantly stimulates ischemia-induced cardiomyocytes apoptosis by targeting Notch1.
心肌细胞凋亡发生在心肌缺血期间。本研究旨在确定微小RNA-34a（miR-34a）在缺血诱导的心肌细胞凋亡中的作用。主要方法是，通过结扎冠状动脉左前降支使SD大鼠遭受心肌缺血。大鼠发生心肌梗死后，HE染色和TUNEL染色证实凋亡显著增加。miR-34a的表达明显上调，而Notch1的表达下调。心肌中观察到半胱天冬酶-3增加，Bcl-2/Bax比值降低。在本研究的心肌细胞缺血缺氧模型中也观察到了类似结果。当对大鼠心肌细胞进行血清饥饿和微需氧系统处理时，凋亡相关蛋白显著增加。然而，在血清饥饿和缺氧处理前将miR-34a抑制剂转染到心肌细胞中，可以增加Bcl-2/Bax比值并下调半胱天冬酶-3的表达，从而防止心肌细胞凋亡。与上述情况相反，转染miR-34a模拟物上调miR-34a表达会导致Notch1减少，凋亡相关蛋白明显增加，而Notch1的上调可刺激miR-34a诱导的凋亡。机制上，我们证明Notch1是miR-34a的直接靶点。总之,我们目前的结果表明，miR-34a通过靶向Notch1显著刺激缺血诱导的心肌细胞凋亡。
