摘要
目的观察血管紧张素Ⅱ1型受体(AT1)拮抗剂缬沙坦对多柔比星诱导的扩张型心肌病(DCM)大鼠心肌的预保护作用,并探讨其可能机制。方法 60只SD大鼠随机分为正常对照组20只(生理盐水腹腔内注射),DCM组20只(多柔比星每周2 mg/kg腹腔内注射)和缬沙坦预处理组20只(多柔比星每周2 mg/kg腹腔内注射)。缬沙坦预处理组在造模的同时给予缬沙坦30 mg.kg-1.d-1灌胃,而正常对照组和DCM组则给予同体积的生理盐水灌胃。8周后行心脏超声和血流动力学检测,取各组大鼠心肌组织行苏木素-伊红(HE)染色和VG染色,测定心肌胶原含量(CVF),并测定心肌组织中肌浆网钙泵(SERCA2a)、钙释放通道(RyR2)、受磷蛋白(PLB)和钠钙交换蛋白(NCX1)的蛋白表达水平。结果与正常组相比,DCM组心功能明显下降(P<0.05),CVF含量明显增多(P<0.01),SERCA2a、RyR2蛋白表达水平显著降低(P<0.05),PLB、NCX1蛋白表达水平显著升高(P<0.05),和DCM组相比,缬沙坦预处理组心功能明显改善(P<0.05),CVF含量明显下降(P<0.05),SERCA2a、RyR2蛋白水平增高(P均<0.05),NCX1、PLB蛋白水平显著降低(P<0.05)。结论预防性给予缬沙坦能减轻多柔比星对钙调蛋白的下调作用和致心力衰竭作用,对防止扩张型心肌病的发生、发展有重要意义。
Objective To observe the protective effects of pretreating with angiotensin Ⅱ type 1 receptor blocker（AT1） and valsartan on the cardiac function of dilated cardiomyopathy（DCM） in rats induced by doxorubicin and discuss the possible mechanism.Methods Sixty SD rats were divided randomly into 3 groups as follows：the normal control group（injected with physiological saline via intraperitonealy,n=20）,the DCM group（injected with doxorubicin via intraperitonealy,n=20）and the preconditioning group（injected with doxorubicin via intraperitonealy,n=20）.The dose of doxorubicin was 2 mg·kg-1·w-1.Valsartan was administered by daily gavage at a dose of 30 mg·kg-1·d-1 in the preconditioning group accompanied with establishing models.Physiological saline was administered by daily gavage in the normal control group and the DCM group.Eight weeks later,the echocardiographic measurents and the hemodynamics were obtained,the histopathological characteristics of cardiac muscle were observed by HE and VG dyeing,the protein of SERCA2a,RyR2,PLB and NCX1 in cardiac muscle were determined by methods of Western blot respectively.Results Compared with the normal control group,cardiac function in the DCM group decreased（P0.05）,the CVF increased significantly（P0.05）,the protein levels of SERCA2a and RyR2 in the DCM group were significantly decreased（P0.05）,the protein levels of PLB and NCX1 were increased（P0.05）.Compared with the DCM group,cardiac function in the preconditioning group increased（P0.05）,the CVF decreased significantly（P0.05）,the protein levels of SERCA2a and RyR2 increased significantly（P0.05）while the protein levels of PLB and NCX1 decreased significantly（P0.05）.Conclusion Pretreating with valsartan can attenuate ventricular remodeling and partly normalize contractile function by regulating the calmodulin level in rats with dilated cardiomyopathy.Furthermore,pretreating with valsartan may have important significance in restraining the development of DCM.
基金
江苏省镇江市科技局社会发展项目(SH2007032)
