黄芪多糖对异丙肾上腺素诱导的心肌肥厚大鼠内皮功能的影响

Effects of Astragalus polysaccharides on endothelial function in rats with myocardial hypertrophy induced by isoproterenol

目的观察黄芪多糖(APS)对异丙肾上腺素(ISO)诱导的心肌肥厚大鼠内皮功能的保护作用及其机制。方法 ip 10 mg/kg ISO制备大鼠心肌肥厚模型,60只SD大鼠随机分为6组:对照组,模型组,APS200、400、800mg/kg组,阳性药(普萘洛尔40mg/kg)组,每组10只。各给药组连续ig给药2周,并于给药1 d后ip ISO 2周,对照组给了予等体积的生理盐水。末次给药后禁食12 h,取血,分离循环内皮细胞(CEC)并计数。检测全心质量指数(HMI)、左室质量指数(LVMI);取主动脉组织进行氢化乙啡啶(DHE)超氧阴离子染色;Western blotting法检测血管组织p65、Cu/Zn-SOD蛋白表达。结果与对照组比较,模型组HMI、LVMI分别增加了38.41%、44.91%(P<0.01),CEC数目增多(P<0.01),血管超氧阴离子生成量增加,p65蛋白表达增加,Cu/Zn-SOD蛋白表达下降(P<0.01)。与模型组比较,APS400、800mg/kg剂量组HMI、LVMI降低(P<0.05),CEC数目减少(P<0.01),血管壁超氧阴离子生成减少,p65表达下降,Cu/Zn-SOD蛋白表达升高(P<0.05、0.01)。结论 APS可能通过降低血管壁超氧阴离子生成,升高Cu/Zn-SOD表达,降低p65表达,改善血管炎症和氧化应激状态,保护心肌肥厚大鼠血管内皮功能。

Objective To investigate the protective effect of Astragalus polysaccharide （APS） on endothelial function in rats with cardiac hypertrophy induced by isoproterenol （ISO）. Methods ISO （10 mg/kg） was given by ip injection to set a myocardial hypertrophy model. Sixty SD rats were randomly divided into six groups （n = 10）： control, ISO model, ISO ＋ APS 200 mg/kg, ISO ＋ APS 400 mg/kg, ISO ＋ APS 800 mg/kg, and ISO ＋ propranolo140 mg/kg groups. The rats in each group were ig administered for two weeks in a row, and given ISO for two weeks by ip injection from day 2. the rats in control group received an equal volume of normal saline. After the last administration and fasting for 12 h, blood and heart were taken under anesthesia. The circulating endothelial cells （CEC） were isolated and counted. The heart mass index （HMI） and left ventricular mass index （LVMI） were also observed; The level of superoxide anion in aorta tissue was detected by DHE staining; p65 and Cu/Zn-SOD protein expression of vascular tissue was detected by Western blotting. Results Compared with the control group, HMI and LVMI in ISO model group increased by 38.41% and 44.91% （P 〈 0.01）, and an increase in the number of circulating endothelial cells and superoxide anion generation were also found. The expression of p65 protein was increased. The expression of Cu/Zn-SOD was decreased. Compared with the model group, HMI, LVMI, number of circulating endothelial cells, and expression of p65 in APS （400 and 800 mg/kg） treated group were decreased. The production of superoxide anion in vessel wall was also reduced. However, the expression of Cu/Zn-SOD protein was elevated. Conclusion APS improves the vascular endothelial function in cardiac hypertrophy rats possibly through increasing Cu/Zn-SOD protein expression and reducing the superoxide anion generation and p65 expression.