还原型谷胱甘肽对阿霉素致大鼠心脏毒性的保护作用及其机制  

A Study on the Protective Effect of Reduced Glutathione on Adriamycin Induced Cardiac Toxicity in Rats

作　　者：张红欣[1] 韩鲁军[1] 安召伟[1] 许会军[1] 胡智慧[1] 李颖[2] 

机构地区：[1]河北省石家庄市第一医院,河北石家庄050011 [2]河北医科大学附属第四医院,河北石家庄050011

出　　处：《现代生物医学进展》2015年第30期5854-5857,共4页Progress in Modern Biomedicine

基　　金：河北省科技支撑计划项目(石卫科教字(2013)4号)

摘　　要：目的:探讨还原型谷胱甘肽(GSH)对阿霉素所致大鼠心脏毒性的保护作用及其机制。方法:选取40只健康SD大鼠作为实验动物,将其随机分为4组,即GSH(小剂量)组+阿霉素组(小剂量组)、GSH(大剂量)+阿霉素组(大剂量组)、阿霉素组及生理盐水组,每组各10只。上述前3组均给予阿霉素;小剂量组给予GSH 250 mg/kg;大剂量组给予GSH 500 mg/kg;生理盐水组给予相同体积的生理盐水。末次给药24 h后,应用免疫组化学SP法检测大鼠心肌组织中BAX和BCL-2蛋白的表达情况,应用ELISA法测定大鼠血清中CK(肌酸激酶)、CK-MB(肌酸激酶同工酶)、LDH(乳酸脱氢酶)的含量以及心肌组织中超氧化物歧化酶(SOD)、丙二醛(MDA)的活性,并对实验数据进行统计学分析。结果:1与阿霉素组相比,应用GSH干预的大鼠心肌组织中BCL-2的表达显著升高,BAX的表达显著降低,差异均有统计学意义(P<0.05);大、小剂量组间BAX和BCL-2蛋白的表达水平比较无统计学差异(P>0.05);2与阿霉素组相比,GSH干预的大鼠血清CK、CK-MB、LDH水平均显著下降,但大、小剂量组间比较无显著性差异(P>0.05);3与阿霉素组相比,应用GSH干预的大鼠心肌组织MDA水平降低,SOD活力升高(P<0.05),但大、小剂量组间比较无显著性差异(P>0.05)。结论:还原型谷胱甘肽能够抑制阿霉素导致的心脏毒性作用,其作用机制可能与提高心肌组织BCL-2蛋白的表达与SOD水平、降低MDA水平以及BAX蛋白的表达有关。Objective： To investigate the protective effect of reduced glutathione on adriamycin induced cardiac toxicity in rats.Methods： 40 healthy SD rats were selected and randomly divided into the small dose group, big dose group, Adriamycin group and saline group. Small dose group was treated by Adriamycin and GSH（250 mg/kg）. Big dose group was treated by Adriamycin and GSH（500mg/kg）. Adriamycin group was treated by Adriamycin. Saline group was treated by saline. The expressions of BAX and BCL-2proteins in myocardium were tested by SP Immunohistochemistry method after the last administration of 24 h. The serum activity of CK（creatine kinase）, CK-MB（creatine kinase）, LDH（lactate dehydrogenase）, and SOD（superoxide dismutase） as well as MDA in myocardium were measured by Elisa. Results： Compared with the adriamycin group, the BCL-2 expression were higher in different doses of GSH treated groups（P〈0.05）, but the BAX expression were lower,（P〈0.05）; the serum CK, CK-MB, LDH contents were significantly lower（P〈0.05）. MDA levels in myocardium were lower（P〈0.05） and SOD activities were higher（P〈0.05）. However, no significant difference was found in the above index between different doses of GSH treated groups（all P〈0.05）. Conclusion： Reduced glutathione could relieve adriamycin induced cardiotoxicity, which might be related to the improvement of myocardial BCL-2 protein expression and SOD level, decrease of BAX protein expression and activity of MDA.

关 键 词：还原型谷胱甘肽 阿霉素 心脏毒性 

分 类 号：Q95-3[生物学—动物学]