miR-383-3p靶向PTEN/PI3K/Akt/mTOR信号通路对冠心病大鼠内皮细胞凋亡的影响

doi:10.3969/j.issn.1006-6233.2022.12.002

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Abstract Objective: To explore the effect of microRNA-383-3p (miR-383-3p) on endothelial cell apoptosis in rats with coronary atherosclerotic heart disease (CHD) by targeting the gene of phosphate and tension homology deleted on chromsome ten/Phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PTEN/PI3K/AKT/mTOR) signaling pathway. Methods: The SD rats were divided into control group, CHD group, mimic NC group, miR-383-3p mimic group, miR-383-3p mimic+pcDNA3. 1 group, and miR-383-3p mimic+pcDNA3. 1-PTEN group, with 15 rats in each group; except for the control group, rats in the other groups were fed with high-fat diet and injected with pituitrin to construct a CHD model, and the lentivirus solution or plasmid vector was injected into the corresponding group of rats at 24 hours before modeling; quantitative Real-time (qRT-PCR) was used to detect the expression of miR-383-3p in coronary arteries; automatic biochemical analyzer was used to determine the level of blood lipid in rats; enzyme linked immunosorbent assay(ELISA) was used to detect the levels of serum endothelin-1 (ET-1), angiotensin Ⅱ (AngⅡ), vascular endothelial growth factor (VEGF) and nitric oxide (NO); HE staining and TUNEL method were used to observe the pathological changes of coronary artery tissues and endothelial cell apoptosis; dual luciferase reporter gene experiment was used to verify the targeting relationship between miR-383-3p and PTEN; Western blot was used to detect the expression of Bcl-2, Bax and PTEN/PI3K/Akt/mTOR pathway protein in coronary artery tissue. Results: Compared with the control group, the miR-383-3p, high-density lipoprotein cholesterol (HDL-C), VEGF, NO, Bcl-2, p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR levels were significantly reduced in the CHD group, the triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), ET-1, AngⅡ levels, coronary artery tissue pathological damage, endothelial apoptosis index (AI), Bax, PTEN expression were significantly increased (P<0. 05); compared with the CHD group, the miR-383-3p, HDL-C, VEGF, NO, Bcl-2, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR levels were significantly increased in the miR-383-3p mimic group, the TG, LDL-C, TC, ET-1, AngⅡ levels, coronary artery tissue pathological damage, endothelial cell AI, Bax, PTEN expression were significantly reduced (P<0. 05); overexpression of PTEN can reverse the improvement of miR-383-3p overexpression on endothelial cell apoptosis and functional damage in CHD rats; PTEN was the target gene of miR-383-3p. Conclusion: MiR-383-3p can targetingly inhibit the expression of PTEN to activate the PI3K/Akt/mTOR signaling pathway, thereby inhibiting the apoptosis of endothelial cells in CHD rats.

Key words： microRNA-383-3p Gene of phosphate and tension homology deleted on chromsome ten/Phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin CHD Apoptosis

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2022.12.002 OR http://www.hbyxzzs.cn/EN/Y2022/V28/I12/1943

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