Abstract:Objective To observe the effect and mechanism of ivabradine on myocardial fibrosis and myocardial injury in rats with coronary heart disease. Methods 60 SD rats were randomly divided into control group, model group and ivabradine low and high dose groups, 15 rats in each group. In addition to the control group, the other three groups of rats were fed with high-fat diet and injected with vitamin D3 to build a coronary heart disease model. After successful modeling, the rats in the lowdose and high-dose ivabradine group were administered by intragastric administration of ivabradine at 10 mg/kg and 20 mg/kg, once a day for 4 weeks. Ultrasound imaging system detects rat heart function. Enzyme linked immunoassay analyzer was used to measure the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and brain natriuretic peptide (BNP). Hematoxylineosin staining (HE) was used to detect histopathological changes of rat aortic arch and myocardium. Masson staining was used to detect the expression of collagen fibers in myocardial tissue. 〖JP2〗Immunohistochemical staining was used to detect the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), collagen-Ⅰ,collagen Ⅲ. Western blot was used to detect the protein expression levels of TIMP-1, ClearedCaspase3, Bcl2 and Bax in myocardial tissue. Results Compared with the control group, the model group EF and FS decreased, LVDD and LVSD increased (P<0.05), Serum MDA concentration increased, SOD activity decreased, BNP level increased(P<0.05), proportion of plaque area in the aorta increased, the arrangement of myocardial fibers disordered, and myocardial cells appeared hypertrophy, degeneration and necrosis, and there are a lot of blue collagen fibers. The positive expression rate of TIMP1, collagen Ⅰ and collagen Ⅲ in myocardial tissue increased (P<0.05). At the same time, the relative expression of TIMP-1, ClearedCaspase3 and Bax protein increased, and the relative expression of Bcl-2 protein decreased (P<0.05). Compared with the model group, the EF and FS of rats in the lowdose and highdose ivabradine group increased, LVDD and LVSD decreased (P<0.05), MDA concentration decreased, SOD activity increasedand BNP level decreased (P<0.05), the proportion of plaque area in the aorta ; decreased, Myocardial tissue lesions significantly improved, with a small amount of blue collagen fibers; myocardial tissue TIMP-1, collagen Ⅰand collagen Ⅲ positive expression rate decreased (P<0.05). At the same time, the relative expression of TIMP-1, ClearedCaspase3 and Bax protein decreased, and the relative expression of Bcl-2 protein increased (P<0.05). ConclusionIvabradine may have a protective effect on myocardial tissue and alleviate myocardial fibrosis in rats with coronary heart disease.