摘要
目的探讨血管紧张素Ⅱ1型受体阻滞剂(ARB)缬沙坦对扩张型心肌病(DCM)心衰大鼠心肌肌浆网Ca2+-ATP酶(SER-CA2a)及其调控蛋白(PLB)的影响及意义。方法腹腔注射多柔比星建立SD大鼠DCM模型。随机分为DCM组(M组,n=11)、缬沙坦组(V组,n=10)、另设正常对照组(C组,n=10),V组予以缬沙坦30 mg.kg-1.d-1,C组和M组予以生理盐水灌胃,8周后行血流动力学检测,采用RT-PCR和Western-blot法分别检测心肌组织SERCA2a、PLB的mRNA和蛋白含量。结果与正常对照组相比,DCM组左心室压峰值(LVSP)、左室最大压力上升及下降速度(±dp/dtmax)显著下降(均P<0.05),左室舒张末压(LVEDP)显著上升(P<0.05);缬沙坦组LVSP、±dp/dtmax显著高于DCM组(均P<0.05),LVEDP显著低于DCM组(P<0.05);DCM组SERCA2a的mRNA及蛋白含量显著低于正常对照组(均P<0.05),PLB的mRNA及蛋白含量显著高于正常对照组(均P<0.05)。缬沙坦治疗后SERCA2a的mRNA及蛋白含量显著升高(均P<0.05),PLB的mRNA含量显著降低(P<0.05),而PLB蛋白含量无显著改变(P>0.05)。结论缬沙坦改善DCM心功能可以与其部分纠正SERCA2a、PLB的异常有关。
Aim To study the changes of Sarcoplasmic reticulumCa^2＋-ATPase and phospholamban in rats with dilated cardiomyopathy （DCM） and the effect of angiotensin 11 typel receptor blocker（ARB）, valsartan. Methods Models of DCM were established by adriamycin injected via intraperitonealy in SD rats. Rats were randomly divided into 3 groups as follows：DCM group （group M, n = 11 ）, valsartan group （group V, n = 10 ）, control group （group C, n= 10 ）. Valsartan was administered by daily gavage at a dose of 30 mg·k^-1·d^-1 in group V for 8 weeks. Physiological saline was administered in group C and group M. Hemodynamics were obtained after 8 weeks. SER- CA2a,PLB mRNAs and proteins in cardiac muscle respectively were determined by methods of RT-PCR and Western blot. Results Compared with group C, LVSP, ±LVdp/dtmax were significantly decreased （ both P 〈 0.05 ） , while LVEDP was increased in group M （ P 〈 0.05）. In group V, LVSP and ±LVdp/dtmax were significantly higher than those in group M （ both P 〈 0.05 ）, and LVEDP was significantly reduced（P 〈 0.05 ）. In group M, SERCA2a mRNA and protein expression were downregulated（ both P 〈 0.05 ）, and mRNA and protein levels of PLB were significantly higher than those in group C （ both P 〈 0.05 ）. After the treatment of valsartan in group V, SER- CA2a mRNA and protein expression were significantly increased （ both P 〈 0.05 ）, PLB mRNA was remarkably decreased （ P 〈 0.05 ）, however,protein level of PLB did not differ significantly from that in group M （ P 〉 0.05 ）. Conclusion Treatment with valsartan can improve DCM cardiac function by partly normalizing mRNA and protein levels of SERCA2a, PLB in cardiac muscle.
出处
《安徽医药》
CAS
2010年第2期143-146,共4页
Anhui Medical and Pharmaceutical Journal
