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.