磷酸肌酸对阿霉素致大鼠心肌损伤的保护作用及其抗细胞凋亡的实验研究

Protective effect and mechanism of apoptosis inhibition of phosphocreatine injection to adriamycin-induced myocardium injury in rats

目的通过建立大鼠阿霉素心肌损伤模型,观察磷酸肌酸对阿霉素心肌损伤的保护作用,并研究磷酸肌酸抑制心肌细胞凋亡的机制。方法采用随机分组的方法将40只SD大鼠分为4组。(1)对照组:腹腔注射生理盐水每日一次;(2)阿霉素组:隔日一次腹腔注射阿霉素建立阿霉素心肌损伤模型。(3)阿霉素+磷酸肌酸钠组(小剂量):隔日一次腹腔注射磷酸肌酸钠(200mg/kg),30min后注射阿霉素。(4)阿霉素+磷酸肌酸钠组(大剂量):隔日1次腹腔注射磷酸肌酸钠(300mg/kg),30min后注射阿霉素。用药结束后测定各组大鼠血清、心肌组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性,血清中肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)含量变化。取心肌组织HE染色,观察大鼠心肌病理形态学变化。免疫组织化学染色方法检测各组心肌组织中BAX、BCL-2蛋白表达情况。结果两组加入磷酸肌酸钠大鼠脂质过氧化产物MDA含量减少,心肌抗氧化酶SOD及CAT活性增加,血清中CK、CK-MB含量减少,与阿霉素组比较有统计学意义(P<0.05)。免疫组化结果显示,磷酸肌酸钠组大鼠心肌促凋亡蛋白BAX表达减弱,抗凋亡蛋白BCL-2表达增强,且与阿霉素组比较有意义(P<0.05)。给予不同剂量磷酸肌酸钠的两组大鼠,各项检测指标未见差异(P<0.05)。结论磷酸肌酸通过增强抗氧化酶系统的功能,降低阿霉素引起的氧化应激损伤,抑制自由基引起的心肌细胞凋亡,起到保护心脏功能的作用。

【Objective】 To establish rat models of adriamycin-induced myocardium injury,in order to observe the protective effect and mechanism of apoptosis inhibition of phosphocreatine（PCr） injection in rats.【Methods】 Thirty SD rats were randomLy divided into four groups.control group,normal saline was ip injected everyday.The adriamycin（ADR） group,the rat model of myocardium injury was made by injecting adriamycin into the pleural every other day.ADR with PCr sodium（small dose）group,after intraperitoneal injection of PCr sodium（200mg/kg） 30 minutes,adriamycin was injected every other day.ADR with PCr sodium（large dose）group,after intraperitoneal injection of PCr sodium（300mg/kg） 30 minutes,adriamycin was injected every other day.After the end of drugs,the contents of malondialdehyde（MDA）,the activities of catalase（CAT）、superoxide dismutase（SOD） in serum and myocardial were determined.at the same time,the contents of creatine kinase（CK） and creatine kinase mass（CK-MB） were measured.To observe the changes of rats myocardial pathological with HE and the expression of BCL-2、BAX protein was determined with immunohistochemical method.【Results】 Compared with adriamycin group（P0.05）,the contents of MDA、CK、CK-MB were decreased,but the activities of CAT and SOD were increased in two groups joined PCr sodium.Immunohistochemical results show：compared with adriamycin group（P0.05）,the expression of Bax protein was low,but the expression of BCL-2 protein was high in PCr group.Detection indexes were no difference in different doses PCr sodium groups（P0.05）.【Conclusion】 PCr can protect the function of heart by enhancing antioxidant system,reduce adriamycin-induced oxidative stress damage,and inhibiting myocardial cell apoptosis of free radial-induced.