丹参酮ⅡA对自发性高血压大鼠心肌纤维化的影响

Inhibition of tanshinone ⅡA on myocardial fibrosis in spontaneously hypertensive rats

目的:研究丹参酮ⅡA(TSN)对于自发性高血压大鼠(SHR)心肌纤维化的影响及其作用机制。方法:24只8周龄SHR大鼠随机分为3组:模型组,丹参酮组,缬沙坦组。另有8只同周龄Wistar大鼠为正常组。给予相应的药物治疗4周后,测量鼠尾血压和心室质量,用VG染色检测心肌胶原容积分数(CVF),并用RT-PCR法检测心肌基质金属蛋白酶-2(MMP-2),MMP-9及基质金属蛋白酶组织抑制因子-2(TIMP-2)的表达。结果:模型组血压、心室质量、心室质量指数、CVF均显著高于其他组(P<0.01);心肌TIMP-2、MMP-2和MMP-9mRNA表达显著升高(P<0.05)。经丹参酮和缬沙坦治疗4周后,其血压、心室质量、心室质量指数、CVF,心肌TIMP-2,MMP-2和MMP-9均较模型组亦有不同程度的降低(P<0.05,P<0.01)。结论:TSN能够降低血压、抑制心肌纤维化,其机制可能与其降低心肌组织MMP-2、MMP-9、TIMP-2的表达和改善MMP/TIMP的平衡有关。

Objective： To study the effects of tanshinone on myocardial fibrosis in spontaneously hypertensive rats （ SHR ） and the mechanism. Methods： Twenty four male SHR were randomly divided into positive control group, tanshinone group and valsartan group. Eight male Wistar rats were as a normal control group. After 4 weeks intervention, blood pressure of the rat tail, weight of myocardium were measured,the collagen volume fraction（CVF） in the myocardial tissues were calculated by VG staining and the expression of TIMP-2, MMP-2,MMP-9 mRNA were determined by reverse transcription polymerase chain reaction（RT-PCR）. Results： The blood pressure, ventricular mass, ventricular mass index and CVF of positive control group were higher than other groups （P〈0.01）. The expressions of TIMP-2, MMP-2 and MMP-9 mRNA in positive control group also increased significantly than that in other groups （P〈0.05）. After 4 weeks intervention, the blood pressure （P〈0.01）, ventricular mass, ventricular mass index （P〈0.05） and CVF （P〈0.01） of tanshinone group and valsartan group were lower than positive control group. The expressions of TIMP-2, MMP-2 and MMP-9 mRNA in tanshinone group and valsartan group also decreased significantly than that in positive control groups （P〈0.05）. Conclusion： Tanshinone could depress blood pressure and inhibit myocardial fibrosis of SHR, which may be by suppressing the expression of MMP-2, MMP-9, TIMP-2 and improving the balance of TIMPs and MMPs.