关键词: 冠心病, 疾病模型, 动物, 成纤维细胞生长因子2, 成纤维细胞生长因子受体1, 微小RNA-186-5p, 炎症反应, 内皮细胞损伤

Abstract: Objective　To investigate the effect of microRNA-186-5p (miR-186-5p) on vascular endothelial cell injury and fibroblast growth factor 2 (FGF2)/fibroblast growth factor receptor 1 (FGFR1) signaling pathway in model rats with coronary heart disease (CHD). Methods　A total of 48 male SD rats were divided into the control group, the model group, the miR-186-5p inhibitor group and the miR-186-5p inhibitor NC group (n=12). Except for the control group, rats in the other groups were all constructed CHD models and given corresponding interventions for 4 weeks. The serum levels of left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and endothelin-1 (ET-1) were measured in the four groups of rats. HE staining was used to observe the pathological changes of coronary artery in each group. Western blot assay was used to detect the expression levels of FGF2 and FGFR1 proteins in rat coronary artery. The double luciferase was used to verify the target relationship between miR-186-5p and FGF2. Results　In the control group, the vascular wall of the coronary arteries of rats was uniform without inflammatory cell infiltration. In the model group and the miR-186-5p inhibitor NC group, vascular endothelial cells arranged disorderly and inflammatory cells infiltrated obviously. Compared with the model group, less pathological changes and less inflammatory cell infiltration were found in the miR-186-5p inhibitor group. Compared with the control group, the contents of LVEF, LVFS, HDL-C, NO, the protein expression levels of FGF2 and FGFR1 were significantly decreased in the model group, and the levels of TC, TG, LDL-C, IL-1β, IL-6, TNF-α and ET-1 were significantly increased (P＜0.05). Compared with the model group and the miR-186-5p inhibitor NC group, the contents of LVEF, LVFS, HDL-C, NO, the protein expression levels of FGF2 and FGFR1 were significantly increased, and the levels of TC, TG, LDL-C, IL-1β, IL-6, TNF-α and ET-1 were significantly decreased in the miR-186-5p inhibitor group (P＜0.05). There were no significant differences in the above indicators between the model group and the miR-186-5p inhibitor NC group (P＞0.05). The results of double luciferase assay confirmed that miR-186-5p had a targeted binding site with FGF2. Conclusion　The down-regulation of miR-186-5p can reduce inflammatory reaction and vascular endothelial cell injury in CHD rats, which is related to the activation of FGF2/FGFR1 signaling pathway.

Key words: coronary heart disease, disease models, animal, fibroblast growth factor 2, fibroblast growth factor receptor 1, miR-186-5p, inflammatory response, endothelial cell injury