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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 (GSH) on doxorubicin-induced cardiotoxicity in rats and its mechanism. Methods: Forty healthy SD rats were selected as experimental animals, which were randomly divided into 4 groups: GSH (low dose) + doxorubicin (low dose), GSH (high dose) + doxorubicin High-dose group), doxorubicin group and saline group, each group of 10. The first three groups were given doxorubicin; low-dose group given GSH 250 mg / kg; high-dose group given GSH 500 mg / kg; saline group given the same volume of saline. Immunohistochemical SP method was used to detect the expression of BAX and BCL-2 protein in rat myocardium 24 h after the last administration, and the levels of CK (creatine kinase), CK-MB Kinase isoenzyme, lactate dehydrogenase (LDH) and the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were measured. The experimental data were statistically analyzed. Compared with doxorubicin group, the expression of BCL-2 in myocardium of GSH-treated rats was significantly increased and the expression of BAX was significantly decreased (P <0.05) Compared with doxorubicin group, the levels of serum CK, CK-MB and LDH were significantly decreased in GSH-treated rats (P <0.05). There was no significant difference in the expression of BAX and BCL- However, there was no significant difference between the large and small dose groups (P> 0.05). 3 Compared with the doxorubicin group, the level of MDA and the activity of SOD in the myocardium were decreased (P <0.05) There was no significant difference between large and small dose groups (P> 0.05). CONCLUSION: Reduced glutathione can inhibit cardiotoxicity induced by doxorubicin. Its mechanism may be related to the increase of myocardial BCL-2 protein expression, SOD level, MDA level and the expression of BAX protein.