Protective mechanism of overexpression of ilent information regulator 1 on myocardium in mice after heart transplantation

Abstract

Objective To investigate the protective mechanism of overexpression of ilent information regulator 1 (SIRT1) on myocardium in mice undergoing cardiac transplantation. Methods Thirty BALB/c mice were randomly divided into control group and experimental group. The experimental group mice were injected with SIRT1-Flag adeno-associated virus specifically expressed in myocardium via tail vein, while the control group mice were injected with SIRT1-Flag adeno-associated virus via tail vein. After 4 weeks of expression, heterotopic heart transplantation was performed with Cuff vascular anastomosis using mouse hearts as donors and C57BL/6 as receptors. The survival rate of transplanted heart was observed. The levels of inflammatory factors in peripheral blood of recipient mice were analyzed by enzyme linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in peripheral blood were measured by biochemical reaction. The apoptotic level of cardiomyocyte was analyzed by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL). The expression of apoptotic protein in cardiomyocyte was analyzed by Western blotting. Results Compared with the control group, the heart survival time of the experimental group was significantly increased (12.46±3.14) days (P<0.05). Compared with the control group, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in peripheral blood [ (189.10±15.39), (209.44±10.98), (59.21±9.90) mmol/L], IL-1β, IL-6 and TNF-α [ (55.12±11.32), (41.32±9.21), (29.44±7.80) mmol/L] in the experimental group were significantly down-regulated (P<0.05). Compared with the control group, SOD and MDA levels in peripheral blood [ (6.19±1.20) (3.44±0.76) mmol/L], SOD (3.09±0.89) U/ml in peripheral blood of mice in the experimental group significantly increased and MDA (2.01±0.45) μmol/L in peripheral blood of mice in the experimental group significantly decreased (P<0.05). Compared with the control group, the myocardial apoptotic index of the experimental group was significantly decreased (P<0.05). Compared with the expression levels of cysteinyl aspartate-specific protease-3 (Caspase-3) and B cell lymphoma/leukemia-2 (bcl-2) in the control group, the expression of Caspase-3 in the myocardium of the experimental group was significantly down-regulated, while the expression of bcl-2 was significantly up-regulated (P<0.05). Conclusion Overexpression of SIRT1 in myocardial tissue can significantly reduce the levels of inflammation, oxidative stress and apoptosis of transplanted heart, and prolong the survival time of transplanted heart. Key words: Ilent information regulator 1; Heart transplantation; Inflammation; Oxidative stress; Apoptosis