Su Dan, Yan Hao-ran, Zhang Bei-bei, Wu Da-zheng, Dai Ya-lei
Medical College of Tongji University, Shanghai 200092, China.
Zhong Yao Cai. 2009 Jan;32(1):85-8.
To investigate the effects of Astragalus membranaccus (As) on cardiac function and SERCA2a gene expression in left ventricular tissues of rats with chronic heart failure.
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 + Captopril (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/dt(max) 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.
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.
As can ameliorate abnormity of cardiac function, especially diastoilc function in rats with pressure overload-induced heart failure, and that may be partly related to its up-regulation of SERCA2a gene expressions in left ventricular tissues.
探讨黄芪对慢性心力衰竭大鼠心功能及左心室组织中肌浆网Ca2+-ATP酶2a(SERCA2a)基因表达的影响。
采用腹主动脉缩窄法制备心力衰竭大鼠模型,将60只雄性SD大鼠分为假手术组(Sham)、主动脉缩窄模型组(Model)、模型+黄芪组(20 g/kg)和模型+卡托普利组(0.05 g/kg)。术后第13周开始灌胃给药,连续给药12周后检测大鼠血流动力学指标,包括左心室收缩压(LVSP)、左心室舒张末压(LVEDP)及左心室内压最大上升/下降速率(±LVdp/dtmax)。采用半定量逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法(Western blot)分别检测左心室组织中SERCA2a mRNA和蛋白表达,以甘油醛-3-磷酸脱氢酶(GAPDH)mRNA和蛋白表达为内参进行标准化。
模型组大鼠LVSP和LVEDP明显升高(P<0.01或P<0.001)。卡托普利和黄芪均能抑制LVSP(P<0.05或P<0.01)和LVEDP(P<0.05或P<0.01)的升高。RT-PCR和Western blot结果显示,与假手术组比较,模型组大鼠左心室组织中SERCA2a基因表达明显下调(P<0.05);黄芪能上调SERCA2a基因表达(P<0.05),而卡托普利对其无明显影响。
黄芪可改善压力负荷过载所致心力衰竭大鼠的心功能异常,尤其是舒张功能,其机制可能与上调左心室组织中SERCA2a基因表达有关。