黄芪甲苷保护阿霉素心肌损伤的抗氧化机制研究

Possible mechanisms for the protective effect of Astragaloside on doxorubicin-induced cardiotoxicity

目的观察黄芪甲苷对大鼠阿霉素心肌损伤的保护作用,并探讨其抗氧化作用机制。方法SD大鼠随机分5组,空白对照组(C组),阿霉素组(ADR组),阿霉素+黄芪甲苷低剂量组(ADR+L),阿霉素+黄芪甲苷中剂量组(ADR+M),阿霉素+黄芪甲苷高剂量组(ADR+H)。C组盐水,余组阿霉素腹腔注射。ADR+L、ADR+M、ADR+H组不同剂量黄芪甲苷灌胃,C、ADR组羧甲基纤维素钠灌胃。观察生存率;血浆脑钠肽(BNP)浓度;心肌谷胱甘肽过氧化物酶(GSHPx)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)活力;检测CuZnSOD蛋白水平及mRNA水平表达。结果①大剂量黄芪甲苷可以保护阿霉素心肌损伤。与ADR组比较,ADR+H组大鼠的生存率明显提高(P<0.01),血浆BNP浓度明显下降(P<0.01)。②大剂量黄芪甲苷通过增加心肌抗氧化酶活力,增强心肌组织抗氧化酶mRNA转录水平以及蛋白质表达水平发挥其保护作用,且呈剂量依赖性。结论黄芪甲苷从多个环节发挥其抗氧化能力,对阿霉素性心肌损伤具有保护作用,为临床治疗药物性心肌病提供新的思路。

Objectives To study the protective effect of Astragaloside on cardiotoxicity induced by doxorubicin （ADR） and its mechanism. Methods Fifty SD rats were randomized into five groups （n = 10） ： control group （C）, ADR group, ADR ＋ L group, ADR ＋ M group, ADR ＋ H group. The control group was given normal saline by intraperitoneal injection, while the other four groups were given adriamycin by intraperitoneal injection every other day. ADR ＋ L group, ADR ＋ M group and ADR ＋ H group were given multiple astragaloside by gavagc at three different dosages, while the control and ADR control groups were given CMC-Na by garage for six times.Every group＇s survival rate, plasma BNP and GSH-Px, CAT, SOD of rat myocardium were determined. The expression levels of Cu-Zn-SOD protein and mRNA were detected. Results The survival rate was significantly improved in SD rats treated with large dose of astragaloside than that in the ADR group （P 〈 0.01） . Large dose of astragaloside significantly induced plasma BNP （P 〈 0.01）, enhanced the expression level of Cu-Zn-SOD protein and mRNA, upregulated the activities of GSH-Px, CAT and SOD than that of the ADR group. Conelusions Astragaloside have multiple ways to antioxidation which may decrease myocardium injury in rat and protect the myocardium. It may be partly caused by reducing oxygen radical and inhibiting oxidative stress. It is a new idea for cardiomyopathy induced by drug.