The Therapeutic Role of Slit2 in Anti-fibrosis, Anti-inflammation and Anti-oxidative Stress in Rats with Coronary Heart Disease.

Abstract

To investigate the efficacy of Slit2 in the rats with coronary heart disease (CHD). CHD model were constructed by feeding high-fat food and injecting with pituitrin in rat, followed by recombinant Slit2 treatment, and then the cardiac function was evaluated by echocardiography, and the indicators concerning the cardiomyocyte injury markers and lipoprotein status and oxidative stress were measured. The Slit2 expression in the heart tissues was identified by immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect inflammatory cytokines, H2DCFDA staining to determine the ROS generation in heart tissues, Masson trichrome staining to observe myocardial fibrosis, and qRT-PCR and Western blotting to detect gene and protein expressions. Slit2 decreased the levels of LDH, CK-MB, cTnI, TG, TC and LDL-C and increased HDL-C level in CHD rats. In the normal heart tissues, Slit2 expression was significantly lower in cardiomyocytes than cardiac fibroblasts. Furthermore, the expressions of VCAM-1, ICAM-1, fibronectin and TGF-β1 were increased in the heart tissues of CHD rats with the obvious myocardial fibrosis, which were dose-dependently reversed by recombinant Slit2. In addition, recombinant Slit2 also dose-dependently increased the activity of NO, SOD, CAT and GSH-Px, and decreased TNF-α, IL-6, MCP-1, MDA and ROS in CHD rats. Slit2 was downregulated in myocardial tissue and plasma of CHD rats. Recombinant Slit2, by regulating the level of blood lipid, can relieve the myocardial fibrosis, inflammation and oxidative stress in CHD.