Xu Zhaoyan, Mo Yuanxi, Li Xinyi, Hong Wanzi, Shao Sisi, Liu Yaoxin, Shu Fen, Jiang Lei, Tan Ning
Department of Cardiology, the Second School of Clinical Medicine, The First People Hospital of Foshan, Southern Medical University, Guangzhou, China.
Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Front Cell Dev Biol. 2021 Nov 8;9:773381. doi: 10.3389/fcell.2021.773381. eCollection 2021.
Myocardial ischaemia/reperfusion (I/R) injury is still a major challenge in clinical treatment. The role of long non-coding RNA (lncRNA) in the regulation of myocardial I/R injury still needs to be elucidated. The primary isolated neonatal mousse cardiomyocytes and adult mice were used to construct a myocardial ischemia-reperfusion model. qRT-PCR is used to verify gene expression in myocardial tissue and myocardial cells. The effect of AK035396 in primary cardiomyocytes and mouse myocardium was confirmed by TUNEL staining and flow cytometry experiments. RNA pulldown and Western blot were used to identify AK035396 interacting proteins. The expression of apoptosis-related proteins was identified by qRT-PCR and Western blot. and MIRI models, AK035396 was up-regulated after myocardial infarction. Functional studies have shown that knockdown of AK035396 reduces the apoptosis of primary cardiomyocytes and mouse myocardial tissue. AK035396 directly interacts with Mterf1 and inhibits the level of Mterf1. Further experiments have shown that inhibiting Mterf1 will promote the expression of mitochondrial genes COXII and CYTb and cause cell apoptosis. AK035396 plays an important role in myocardial ischaemia-reperfusion injury by regulating the Mterf1-COXII/CYTb pathway.
心肌缺血/再灌注（I/R）损伤仍是临床治疗中的一大挑战。长链非编码RNA（lncRNA）在心肌I/R损伤调节中的作用仍有待阐明。使用原代分离的新生小鼠心肌细胞和成年小鼠构建心肌缺血再灌注模型。采用qRT-PCR验证心肌组织和心肌细胞中的基因表达。通过TUNEL染色和流式细胞术实验证实了AK035396在原代心肌细胞和小鼠心肌中的作用。采用RNA下拉和蛋白质印迹法鉴定与AK035396相互作用的蛋白。通过qRT-PCR和蛋白质印迹法鉴定凋亡相关蛋白的表达。在心肌梗死和心肌缺血再灌注损伤（MIRI）模型中，心肌梗死后AK035396上调。功能研究表明，敲低AK035396可减少原代心肌细胞和小鼠心肌组织的凋亡。AK035396直接与Mterf1相互作用并抑制Mterf1的水平。进一步实验表明，抑制Mterf1会促进线粒体基因COXII和CYTb的表达并导致细胞凋亡。AK035396通过调节Mterf1-COXII/CYTb途径在心肌缺血再灌注损伤中起重要作用。
