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Published on: July 31, 2012
Propofol Protects Rat Cardiomyocytes from Anthracycline-Induced Apoptosis by Regulating MicroRNA-181a In Vitro and In
Hongwei Zhao1,2,3, Xiaobei Zhang1,2,3, Ying Zheng1,2,3
1Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
Abstract:
We aimed to evaluate the cardioprotective effect and mechanism of propofol in anthracycline-induced cardiomyocyte apoptosis. We selected the rat myocardial cell line, H9c2, and primary cardiomyocytes for in vitro study. The cardiomyocytes were treated with vehicle, Adriamycin® (ADM), propofol, or a combination of ADM and propofol. The proportion of apoptotic cells and the expression of miR-181a were detected by flow cytometry and real-time PCR, respectively. Luciferase assays were performed to explore the direct target gene of miR-181a. In vivo assay, rats were randomly divided into different treatment groups. The apoptosis index was determined by TUNEL staining, and the expression of miR-181a and STAT3 in heart tissue was detected. The antiproliferative effect of ADM alone was significantly greater than that of ADM plus propofol. A significantly greater decrease in the proportion of apoptotic cells and in miR-181a expression was observed in the combination treatment group compared with that in the ADM groups in vitro and in vivo. The loss-of-function of miR-181a in H9c2 of ADM treatment resulted in increased Bcl-2 and decreased Bax. MiR-181a suppressed Bcl-2 expression through direct targeting of the Bcl-2 transcript. Propofol reduced anthracycline-induced apoptosis in cardiomyocytes via targeting miR-181a/Bcl-2, and a negative correlation between miR-181a and Bcl-2 was observed.
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