华蟾素拮抗阿霉素心脏毒性及其作用机制

Effects of Cinobufacini on Adriamycin-Induced Cardiotoxicity and Its Mechanisms

目的研究华蟾素拮抗阿霉素的心脏毒性,探讨其可能的作用机制。方法将SD大鼠随机分为阿霉素组、右丙亚胺组、华蟾素低剂量组、华蟾素高剂量组,各组均予阿霉素2mg/kg隔天腹腔注射,建立心肌损伤模型,并给予相应药物干预处理。观察各组大鼠一般情况,检测超氧化物歧化酶(SOD)、丙二醛(MDA)、心肌酶(LDH、GOT、CK),观测心肌病理的改变。结果与阿霉素组比较,华蟾素低剂量组可以促使大鼠SOD活性显著升高(P<0.01),MDA水平显著降低(P<0.05),促使LDH水平显著降低(P<0.01);可以减轻心肌细胞颗粒变性、炎性细胞浸润等组织损伤,保护线粒体等重要细胞器。右丙亚胺组与华蟾素低剂量组比较无显著差异,华蟾素高剂量组未能获得与低剂量组相同的结果。结论华蟾素通过提高SOD,清除自由基,抑制脂质过氧化反应,可以拮抗阿霉素所致的心脏毒性。

Objective To study the protective effects of cinobufacini on adriamycin-induced cardiotoxicity and its mechanisms. Methods SD rats were randomly divided into adriamycin group, dexrazoxane group, low-dose cinobufacini group and high-dose cinobufacini group. Two mg/kg of Adriamycin was injected to induce myocardium injury model. Superoxide disutase （SOD）, malon diadehyde （MDA） and the myocardial enzyme （LDH, GOT, CK） were detected. The pathological lesion of myocardium was observed. Results Compared with adriamycin group, low-dose cinobufacini group could increase SOD activities（P〈O.05） and decrease MDA content（P〈0.05）, decrease LDH （P〈0.05）, relieve degeneration of myocardial cells and infiltration of inflammatory cells and protect mitochondria. There was no significant difference between dexrazoxane group and low-dose cinobufacini group. High-dose cinobufacini group did not act as low-dose group. Conclusion Cinobufacini can inhibit adriamycin-induced cardiotoxicity by increasing SOD, decreasing free radicals and inhibiting lipid peroxidation.