Effects of Promethazine on Proliferation and Apoptosis of Myocardial Cells in Rats with Myocardial Ischemia-Reperfusion Injury Through PI3K/Akt Signaling Pathway

Abstract

Objective: To assess promethazine's effect on myocardial cells in rats with myocardial ischemiareperfusion injury (MIRI). Methods: The rat MIRI model was established and treated as the ischemia group. MIRI rats were treated with promethazine and included as the drug group. Rats only undergoing thoracotomy were enrolled as the control group. The physiological function of heart was assessed using the ultrasound cardiotachograph, and the apoptosis and proliferation of myocardial cells were detected using TUNEL assay and Ki67 staining, respectively. Moreover, the expressions of Caspase-3, Bcl-2, PI3K, GSK-3, PDK-1 and PKB were determined via Western blotting and qPCR. Results: There were significant differences in cardiac function indexes [left ventricular enddiastolic diameter (LVEDd), left ventricular end systolic diameter (LVESd), ejection fraction (EF) and fractional shortening (FS)] among the three groups (p= 0 002, 0.004, 0.025 and 0.012), and ischemia group had the highest LVEDd [(8.73± 0.31) mm] and LVESd [(7.98± 0.37) mm] and lowest EF [(42± 3.8)%] and FS [(40.3± 2.8)%]. The number of apoptotic myocardial cells was significant higher in ischemia group than control ( p< 0 05), while it was significantly declined after treatment with promethazine ( p< 0 05). Caspase-3 was significantly upregulated and Bcl-2 was downregulated in ischemia group which were all significantly reversed in drug group. Besides, Ki67 level was significantly reduced in ischemia group compared to control and higher in drug group than ischemia group, indicating that drug treatment increased cell proliferation ability. The levels of PI3K, GSK-3 and PKB in myocardial tissues were significantly declined in ischemia group and elevated after the treatment with promethazine without difference of PDK-1 level in myocardial tissues among the three groups. Conclusion: Promethazine inhibits apoptosis and promotes proliferation of myocardial cells in MIRI rats through PI3K/Akt signaling pathway.