Abstract: Abstract: Objective To analyze the effect of PKD1/HDAC5 axis on myocardial repairment in rats with myocardial infarction. Methods Forty male Wistar rats were divided into four groups: sham-operated (Sham) group, model group,PKD1 treatment group (2 mg·kg-1 ·d-1 PKD1) and CID755673 blocker group (2 mg·kg-1 ·d-1 PKD1+10 ng·kg-1 ·d-1 CID755673) according to the rule of random number table. The model group was treated with classical left coronary artery ligation to reproduce the myocardial infarction model, while the sham-operated group underwent thoracotomy without ligation. An equal amount of normal saline was injected in the model group and sham group. All administrations were performed via a tail vein injection every other day for 28 days. The pathological changes of myocardium were analyzed by HE staining, the changes of collagen in myocardial tissue were analyzed by Masson staining, the apoptotic changes of cardiomyocytes were detected by TUNEL method, and the immunohistochemistry and immunoblotting were used to detect the expressions of HDAC5, myocyte enhancer factor 2 (MEF2) and cardiac troponin I (cTn I). Results The pathological results showed that the rat myocardium was normal in the Sham group, no necrosis and inflammatory infiltration, low percentage of collagen, occasional apoptotic myocardial cells, fewer HDAC5 and MEF2 positive cells and a large number of cTn I positive cells. Compared with the Sham group, there were obvious myocardial necrosis, inflammatory infiltration, higher percentage of collagen, apoptotic myocardium and MEF2 positive cells, and less cTn I positive cells in the model group (P＜0.05). Compared with the model group, PKD1 treatment could significantly improve the degree of myocardial necrosis in rats with myocardial infarction, and significantly reduce the proportion of collagen in damaged myocardial tissues, decrease the number of apoptotic myocardial cells and MF2-positive cells (P＜0.05), and increase the number of cTn I-positive cells (P＜0.05), while CID755673 could block the therapeutic effect of PKD1. Conclusion PKD1 combined with HDAC5 might promote myocardial tissue in rats with myocardial infarction, which could be blocked by CID755673.

Key words: myocardial infarction, protein kinases, histone deacetylases, troponin I, apoptosis, myocyte enhancer2