辛伐他汀对一氧化氮缺乏性大鼠心肌肥大的抑制作用及机制探讨

目的:观察辛伐他汀对一氧化氮(NO)缺乏性高血压大鼠心肌肥大的作用并探讨其机制。方法:40只大鼠随机分为对照组、模型组、小剂量和大剂量辛伐他汀组。用一氧化氮合酶抑制剂制备心肌肥大模型。6周后测定大鼠心肌肥大指标和心肌血红素氧合酶(HO)活性。结果:模型组动物心肌明显肥大,辛伐他汀治疗组动物较模型组心肌肥大明显减轻,左心室重量指数(LVMI)、心肌BNP含量和羟脯氨酸含量均显著降低(均P<0.01),心肌HO活性明显升高(P<0.01),心肌HO活性与LVMI、心肌羟脯氨酸含量和心肌BNP含量呈明显负相关。结论:辛伐他汀可抑制NO缺乏性大鼠心肌肥大并诱导心肌HO活性升高,HO1CO通路可能是他汀类药物非降脂作用的重要机制之一。

Effect of simvastatin on cardiac hypertrophy of nitric oxide-depleted rat and its mechanism

Objective:To investigate the effect of simvastatin on cardiac hypertrophy of nitric oxide-depleted rat and its mechanism. Method:Forty male Waster rats were randomly divided into four groups(n=10 in each group). Rats in model group received N-nitro-L-arginine(L-NNA) 7.5 mg peritoneal injection twice daily. Left ventricular function, left ventricular mass index(LVMI) and the content of brain natriuretic peptide, hydroxyproline as well as heme oxygenase activity of heart were measured after six weeks.Result:Rats in model group developed significantly cardiac hypertrophy with reduced left ventricular diastolic function. However, compared with model group, cardiac hypertrophy of rats in simvastatin treatment groups relieved significantly associated with improved left ventricular diastolic function. The marks of cardiac hypertrophy, such as LVMI, the content of BNP and hydroxyproline of heart decreased significantly(P<0.01).Compared with model group , the heme oxygenase(HO) activity of rat heart in simvastatin treatment groups elevated significantly (P<0.01).There is a negtive correlation between HO activity and LVMI, the content of BNP and hydroxyproline of heart respectively.Conclusion:Simvastatin inhibit the cardiac hypertrophy of rat induced by L-NNA and elevate the HO activity of rat heart. HO-1/CO pathway may be one of the important mechanisms of non-lipid lowering effect of statins.