关键词: 瑞舒伐他汀；压力超负荷；心肌肥厚；GATA4

Abstract:

Objective   To discuss the molecular mechanisms of Rosuvastatin (RSV) on regression of myocardial hypertrophy induced by abdominal aortic constriction. Methods   Twenty-eight male Wistar rats were randomly divided into 4 groups: sham-vehicle (SH-V), abdominal aortic constriction-vehicle (AAC-V), abdominal aortic constriction-RSV［4mg/(kg·day)］(AAC-LO), and abdominal aortic constriction-RSV ［10mg/(kg·day)］(AAC-HI). There were 7 rats in each group. From 5 days pre-operation to 4 weeks post-operation, four groups were performed by gavage administration with equal volume of RSV and vehicle. The research was finished 4weeks after the surgery. Echocardiography data, the ratio of LV weight to body weight (LVW/BW) and left ventricle myocyte cross-sectional area were evaluated. Reverse transcription PCR (RT-PCR) was adopted to test ANF and β-MHC mRNA expression levels which were related to myocardial hypertrophy. Western Blots analysis was used to detect GATA4 and phospho-GATA4(Ser105)protein levels in rat myocardial tissue.  Results   Compared to SH-V group, thickness of interventricular septum in diastole (IVSd) , diastolic left ventricular posterior wall thickness (LVPWd), the ratio of left ventricular weight to body weight (LVW/BW) and myocyte cross-sectional area (CSA) were significantly increased (P<0.01) in AAC-V group. In AAC-LO and AAC-HI groups, IVSd, LVPWd and CSA were obviously decreased (P<0.01) and LVW/BW was also decreased (P<0.05) compared to AAC-V group, and there was no significant difference between AAC-LO and AAC-HI groups(P＞0.05). These results indicated that myocardial hypertrophy alleviated.  Left ventricular ejection fraction (LVEF) in AAC rats was significantly decreased compared with SHV group (P<0.01). LVEF in AAC-LO and AAC-HI groups promoted distinctly (P<0.01) compared to AAC-V group (P<0.01). ANF and β-MHC mRNA expressions and phospho-GATA4 (Ser105) protein levels in AAC group were significantly increased compared to SH-V group (P<0.01), and in AAC-LO and AAC-HI groups these indexes were decreased obviously compared to AAC group (P<0.01).   Conclusion   GATA4 may participate in the process of myocardial hypertrophy caused by pressure overload and RSV could reverse pressure overload-induced myocardial hypertrophy by decreasing GATA4 activity.

Key words: Rosuvastatin; Pressure overload; Myocardial hypertrophy; GATA4