金樱子对阿霉素诱导心肌损伤的保护作用及机制

摘要

目的：观察金樱子(Rosa Larigata Michx,RlM)对阿霉素诱导心肌损伤大鼠模型的保护作用及相关机制。方法30只SD大鼠随机分为空白对照组、阿霉素组模型组和金樱子干预组（n=10）。模型组采用阿霉素（15 mg/kg）分6次隔天腹腔注射，金樱子组按每公斤体重给予1～5g金樱子灌胃，空白对照组仅给予等体积生理盐水。处理结束后，观察观察大鼠生存率；ELISA检测血浆脑钠肽（brain natriuretic peptide，BNP）浓度；采用缺口末端标记法检测心肌凋亡细胞。同时观察心肌组织中心肌谷胱甘肽过氧化物酶（glutathion peroxidase，GSH-PX）、过氧化氢酶（hydrogen peroxidase，CAT）、总超氧化物歧化酶（total superoxide dismutase，T-SOD）的活力；实时定量PCR检测铜锌超氧化物歧化酶（CuZn superoxide dismutase，CuZn-SOD）以及bcl-2、bax mRNA表达水平。结果与阿霉素组比较，金樱子可明显提高大鼠的生存率（P<0.01）。阿霉素组大鼠血浆BNP浓度显著增高（P<0.01），金樱子处理后BNP浓度显著降低（P<0.01）。此外，阿霉素组CuZn-SOD蛋白表达水平以及心肌组织GSH-PX、CAT、SOD活力明显降低。金樱子能提高CuZn-SOD蛋白mRNA表达水平以及心肌组织GSH-PX、CAT、SOD活力。阿霉素组心肌细胞凋亡发生率显著增高（P<0.01）；bcl-2基因表达下降，bax基因表达增强，bcl-2/bax mRNA比值降低。高剂量金樱子能降低阿霉素所致心肌细胞凋亡，并增强bcl-2基因表达，降低bax水平。结论金樱子通过多环节发挥抗氧化作用，并具有一定的抗凋亡效应，其作用机制可能与影响bcl-2和bax的表达有关。%Objective To study the protective effect mechanism of Rosa laevigata Michx (RLM) on cardiotoxicity induced by adriamycin in rats. Method 30 SD rats were randomly into control group, doxorubicin group and RLM groups. The control group was injected with normal saline injection, while the model group was injected with adriamycin intraperitoneally at the dosage of 15 mg/kg every other day. For the RLM groups,1~5 g/kg RLM were given after adriamycin injection. The survival rate, plasma BNP was observed. Apoptosis of cardiomyocyte was detected by instituted-labeled DNA (TUNEL). The activity of GSH-PX, CAT and total SOD in the myocardium tissue were also observed. The expression level of CuZn-SOD , bcl-2 and bax were detected by real-time PCR. Results The survival rate was significantly improved in SD rats treated with RLM compared with that in the adriamycin group (P<0.01). The BNP level was increased when treated by adriamycin (P<0.01), and decreased after RLM administration (P<0.01). RLM could also upregulate the expression of the CuZn-SOD mRNA level, and enhance the activity of GSH-PX, CAT and T-SOD compared with that in adriamycin group. Adriamycin could induce myocardial cells apoptosis, as demonstrated by TUNEL. RLM could inhibit adriamycin-induced apoptosis, bax mRNA expression, and increase bcl-2 expression and bcl-2/bax ratio. Conclusion RLM exhibit some antioxidant activity through many stages, and the anti-apoptosis activity may be related to affect the expression of bax and bcl-2 expression.