| Background and Objective: Hypertension is a kind of progressive vascular syndrome caused by many etiopathogenisis, which lead to irreversed reconstruction of cardiovascular system and reflected as increasing in left ventricular wall,ventricular expansion and interstitial fibrosis. Multiple factors participate this pathophysiologic process, which may related with blood pressure and the imbalance of cell proliferation and apoptosis. As a down-regulation factor in cell generation cycle, p21 protein plays an important role in cell proliferation and differentiation. Statins are most widely used to modulate the plasma lipid level in the clinical setting. Recently, several clinical trails have demonstrated that statins has pleiotropic beneficial effects on cardiovascular tissue; much attention about the beneficial effects of statins on myocardial hypertrophy and its possible mechanisms has been attracted by people. The aim of this study is to investigate the effect of atorvastatin (ATV) on p21 expression of left ventricular hypertrophy in SHR and to discuss the underlying mechanisms involved of atorvastatin (ATV) on myocardial hypertrophy of SHR, which may provide proofs for clinical management.Methods: Sixteen male 8-week-old SHR were randomly divided into two groups: SHR group (SHR, n=8, gavaged by distilled water) and atorvastatin group (ATV, gavaged by atorvastatin), and the age-matched Wistar-Kyotorats (WKY) gavaged by distilled water were served as control group (WKY, n=8). Atorvastatin was resolved in 1ml distilled water and was administrated to ATV group by gavage with the daily dose of 50mg·kg-1 for 10 weeks, and rats in SHR groups and WKY groups were given the same amount of distilled water by gavage for 10 weeks. Ten weeks later, all rats were anesthesiated by intraperitoneal injection of sodium pentobarbital and 5ml arterial blood was taken for the determination of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The left ventricle was then isolated along with the ventricle septum (ventricle septum included). The heart weight to body weight ratio (HW/BW) and the left ventricle weight to body weight ratio (LVW/BW) which served as an indication for myocardial hypertrophy were calculated. In addition, rat myocardiums specimens which embedded in paraffin and stained with hematoxylin and eosin (HE) were observed. The distribution of the P21 protein in left ventricular myocardium was observed by immunohistochemistry analysis. The express of P21 mRNA were analyzed by RT-PCR method.Result:After the intervention of atorvastatin:1. Result of blood-fat: compared with WKY group, serum TC, TG, HDL-C and LDL-C levels were statistically higher in SHR group and ATV group (p<0.01). However, no significant differences in serum TC, TG, HDL-C and LDL-C levels were observed between ATV group and SHR group(p>0.05).2. Index of myocardial hypertrophy: In SHR group, myocardial hypertrophy in left ventricle was observed, and HW/BW and LVW/BW were significantly higher than that in WKY group(p<0.01). HW/BW,LVW/BW in ATV groups were decreased remarkable compared with SHR group(p<0.01). 3. Pathomorphology: In WKY group, cardiac muscle cell were spread regularly and no hypertrophy were occurred. In SHR group, cardiac muscle cell were spread of derangement and hypertrophy were occurred. In ATV group treated with atorvastatin, cardiac muscle cell were spread regularly and no significant hypertrophy were observed.4. Result of immunohistochemistry analysis: the positive rate of P21 protein express within cardiac muscle cell in SHR group was markedly decreased(p<0.01). And after the intervention of atorvastatin, the positive rate of P21 protein express within cardiac muscle cell in ATV group were significantly increased compared with SHR group(p<0.01).5. Result of RT-PCR: the level of P21 mRNA express within cardiac muscle cell in SHR group were significantly than that in WKY group(p<0.01). Compared with the SHR group, the level of P21 mRNA express within cardiac muscle cell significantly increased after the intervention of atorvastatin (p<0.01).6. The associations between expression of P21 mRNA in cardiomyocytes and myocardial hypertrophy: the expression of P21 mRNA in cardiomyocytes were negatively correlated with HW/BW (r=-0.709, P<0.0001) and LVW/BW (r=-0.665, P<0.0001).Conclusion: Obviously myocardial hypertrophy and lower expression of P21 were observed in spontaneous hypertensive rat. After the intervention of atorvastatin, the myocardial hypertrophy decreased which accompanied with the higher expression of P21, which may related with amelioration effect of atorvastatin on myocardial hypertrophy.
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