黄芪对慢性心衰大鼠心功能及心肌肌浆网钙泵基因表达的影响

Effects of Astragalus membranaccus on Cardiac Function and SERCA2a Gene Expression in Myocardial Tissues of Rats with Chronic Heart Failure

目的:探讨黄芪对慢性心衰大鼠心功能及心肌肌浆网钙泵基因(SERCA2a)表达的影响。方法:60只大鼠随机分为假手术组、模型组、黄芪组(20 g/kg)和卡托普利组(0.05 g/kg)。采用缩窄腹主动脉法制备慢性心衰模型,造模后第13周开始灌胃给药,连续给药12周后测定大鼠在体血流动力学指标,并采用RT-PCR、Western blot方法检测左室组织SERCA2a基因的表达。结果:模型大鼠左室收缩压(LVSP)、左室舒张末压(LVEDP)均较假手术组显著升高(P<0.01或P<0.001),卡托普利和黄芪均能降低模型大鼠LVSP(P<0.05或P<0.01)、LVEDP(P<0.05或P<0.01);模型组大鼠左心室SERCA2a基因表达较假手术组下调(P<0.05),黄芪能上调模型大鼠SER-CA2a基因表达(P<0.05),而卡托普利对其表达无明显影响。结论:黄芪能改善慢性心衰大鼠心功能障碍,并以改善舒张功能为主,其机制可能与上调心肌SERCA2a基因表达有关。

Objective： To investigate the effects of Astragalus membrartaccus （As） on cardiac function and SERCA2a gene expression in left ventricular tissues of rats with chronic heart failure. Methods ： Heart failure was induced by clipping the abdominal aorta. 60 male SD rats were divided into four groups： sham-operated（ Sham）, aortic stenosis （Model）, Model ＋ As （20 g/kg） and Model ＋ Cap- topril（0. 05 g/kg）. The drugs were administered orally from the 13th week after surgery. Rats were examined after 12 weeks＇ treatment with drugs. The parameters of hemodynamics including LVSP, LVEDP, and ＋ LVdp/dtmax were measured. SERCA2a mRNA and protein expressions in left ventricular tissues were determined by half-quantitative RT-PCR and Western blot normalized to abundance of GAPDH mRNA and portein, respectively. Results： LVSP and LVEDP were obviously enhanced （P 〈0. 01 or P 〈0. 001 ）in model rats in vivo. Both Captopril and As prevented the increase of LVSP（P 〈0. 05 or P 〈0. 01 ）and LVEDP（P 〈0. 05 or P 〈0. 01 ）. RT-PCR and Western blot results demonstrated that SERCA2a gene expression was downregulated（ P 〈 0. 05 ）significantly in model group compared with sham group. As upregulated SERCA2a gene expression （ P 〈 0. 05 ）, whereas Captopril had no effect on that. Conclusion： As can ameliorate abnormity of cardiac function, especially diastoilc function in rats with pressure overload-induced heart failure, and that may be partly ralated to its up-regulation of SERCA2a gene expressions in left ventricular tissues.