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

OBJECTIVE: This study aims to ex- plore the role and the mechanism of Parkin pro- tein in cardiac function and ventricular remodel- ing in myocardial infarction (MI) rats, and to pro- vide a new sight for the treatment of myocardi- al infarction. MATERIALS AND METHODS: Fifty Sprague- Dawley (SD) male rats were randomly divided into 5 groups: sham operation group (Sham group), model group (MI group), low-dose Par- kin group (L-Parkin group), middle-dose Parkin group (M-Parkin group) and high-dose Parkin group (H-Parkin group). The rat model of myo- cardial infarction was established by ligation of the anterior descending branch. Small animal ultrasound was used to measure cardiac func- tion. The myocardial infarct size was observed by triphenyltetrazolium chloride (TTC) staining. The pathological changes of myocardial tissues were observed by hematoxylin-eosin (HE) stain- ing. The myocardial cell apoptosis was detected by TUNEL assay. The mRNA expression of ma- trix metalloproteinase 2 (MMP2), matrix metallo- proteinase 9 (MMP9), tissue inhibitor of matrix metalloproteinase 1 (TIMP1), tissue inhibitor of matrix metalloproteinase 2 (TIMP2) were detect- ed by qRT-PCR. The expression of Parkin pro- tein in myocardial tissue of rats was detected by Western-blot. RESULTS: Compared with MI group, left ven- tricular 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 ven- tricular short axis shortening (FS) and left ven- tricular ejection fraction (EF %) in Parkin over- expression 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). CONCLUSIONS: After treatment with Parkin in myocardial infarction rats, the relevant mRNA levels decreased, the number of apoptotic cells decreased, the myocardial fiber morphology re- turned to normal, the myocardial infarct size decreased, and the cardiac function of rats im- proved. Therefore, Parkin therapy plays an ac- tive role in cardiac function and ventricular re- modeling in myocardial infarction rats.