The role of Parkin protein in cardiac function and ventricular remodeling in myocardial infarction rats.

Abstract

This study aims to explore the role and the mechanism of Parkin protein in cardiac function and ventricular remodeling in myocardial infarction (MI) rats, and to provide a new sight for the treatment of myocardial infarction. Fifty Sprague- Dawley (SD) male rats were randomly divided into 5 groups: sham operation group (Sham group), model group (MI group), low-dose Parkin group (L-Parkin group), middle-dose Parkin group (M-Parkin group) and high-dose Parkin group (H-Parkin group). The rat model of myocardial infarction was established by ligation of the anterior descending branch. Small animal ultrasound was used to measure cardiac function. The myocardial infarct size was observed by triphenyltetrazolium chloride (TTC) staining. The pathological changes of myocardial tissues were observed by hematoxylin-eosin (HE) staining. The myocardial cell apoptosis was detected by TUNEL assay. The mRNA expression of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), tissue inhibitor of matrix metalloproteinase 1 (TIMP1), tissue inhibitor of matrix metalloproteinase 2 (TIMP2) were detected by qRT-PCR. The expression of Parkin protein in myocardial tissue of rats was detected by Western-blot. Compared with MI group, left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) in Parkin overexpressing group were significantly decreased (p<0.05), while the value of left ventricular short axis shortening (FS) and left ventricular ejection fraction (EF %) in Parkin overexpression group were significantly increased (p<0.05). Overexpression of Parkin improved abnormal structure of myocardial tissue, reduced the size of myocardial infarct, made the arrangement of myocardium fibers more neatly and made the stain of myocardial cells more uniformly. Apoptosis index (AI) values were significantly decreased (p<0.05), and MMP2, MMP9, TIMP1 and TIMP2 mRNA levels were significantly decreased (p<0.05), while Parkin protein expression was significantly elevated in a dose-dependent manner (p<0.05). After treatment with Parkin in myocardial infarction rats, the relevant mRNA levels decreased, the number of apoptotic cells decreased, the myocardial fiber morphology returned to normal, the myocardial infarct size decreased, and the cardiac function of rats improved. Therefore, Parkin therapy plays an active role in cardiac function and ventricular remodeling in myocardial infarction rats.