黄芪注射液对左室肥厚大鼠心肌钙超载及肌浆网钙泵表达的影响

目的：探讨黄芪对压力过载致左室肥厚大鼠心肌钙含量及肌浆网钙泵(SERCA2a)表达的影响。方法：采用缩窄腹主动脉法制备压力过载性心肌肥厚模型。大鼠随机分为假手术组，模型组，低、中、高剂量黄芪组(5，10，20 g·kg^-1·d^-1)和卡托普利组(0.05 g·kg^-1·d^-1)。造模后第13周开始灌胃给药，连续12周。测定大鼠左室质量指数(left ventricular mass index, LVMI)和心肌钙含量的变化(原子吸收光谱法)，并检测(RT-PCR，Western blot)大鼠左室组织肌浆网钙泵的表达。结果：黄芪呈剂量依赖性抑制模型大鼠左室质量指数的增加(P<0.01，P<0.001)，其中高剂量黄芪作用与卡托普利相似；黄芪能抑制肥厚心肌组织钙超载(P<0.01)；与假手术组相比，心肌肥厚大鼠左心室SERCA2a 基因表达下调(P<0.05)，高剂量黄芪使之表达上调(P<0.05)，而卡托普利对其表达无明显影响。结论：黄芪对大鼠压力过载性心肌肥厚的抑制作用可能与其减轻心肌钙超载及上调心肌SERCA2a基因表达有关。

Effect of astragalus on calcium accumulation and SERCA2agene expression in myocardial tissues in rats with pressureoverload-induced left ventricular hypertrophy

Objective: To investigate the effect of astragalus (As) on calcium accumulation and SERCA2a gene expression in left ventricular tissues in rats with pressure overload-induced cardiac hypertrophy. Method: cardiac hypertrophy was induced by clipping the abdominal aorta in rats. Male SD rats were allocated to six groups: sham-operrated (Sham), aortic stenosis (Model), model+As-L (5 g·kg^-1·d^-1), model+As-M (10 g·kg^-1·d^-1), model+As-H (20 g·kg^-1·d^-1) and model+captopril (0.05 mg·kg^-1·d^-1, a positive control). The drugs were administered orally from the 13 th week after surgery. Rats were examined after 12 week treatment with drugs. The cardiac hypertrophy was evaluated by left ventricular mass index (LVMI, left ventricular weight/body weight). The calcium content in left ventricular tissue was measured by atomic absorption spectrometry. 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 protein, respectively. Result: The increase of LVMI was dose-dependently lessened by As (P<0.01, P<0.001). The effect of As-H was similar to that of Captopril. As markedly attenuated calcium accumulation in myocardial tissure (P<0.01). RT-PCR and Western blot results demonstrated that SERCA2a gene expressions were downregulated (P<0.05) significantly in model group compared with sham group. As-H upregulated SERCA2a gene expressions (P<0.05), whereas Captopril had no effect on that. Conclusion: The inhibition of As on left ventricular hypertrophy induced by pressure overload in rats may partly contribute to its attenuation of calcium accumulation and up-regulation of SERCA2a gene expressions in left ventricular tissues.