右丙亚胺对表柔比星诱导大鼠心肌损伤干预机制研究

Function and mechanism of dexrazoxane interventing myocardial damage induced by epirubicin in rats

目的:比较不同剂量右丙亚胺对表柔比星诱导大鼠心肌损伤的干预作用及可能机制。方法:35只SD大鼠随机分5组,每组7只。对照组:于大鼠双侧腹腔分别注射生理盐水5mL/kg,间隔时间为30min,隔日1次,共4次(7d);模型组(表柔比星+生理盐水):大鼠腹腔内注射表柔比星4.5mg/kg,隔日1次,共4次(7d),注射表柔比星前30min于另一区域腹腔内注射生理盐水5mL/kg;表柔比星+低、中、高剂量右丙亚胺组:大鼠腹腔内注射表柔比星4.5mg/kg,隔日1次,共4次(7d),注射表柔比星前30min于另一区域腹腔内注射右丙亚胺45、67.5和90mg/kg,隔日1次,共4次(7d)。处死大鼠后检测各组大鼠心肌组织微量丙二醛(MDA)含量、总超氧化物歧化酶(T-SOD)活性、血浆乳酸脱氢酶(LDH)及肌钙蛋白I(cTnI)水平,观察心肌组织病理形态学改变及心肌细胞凋亡情况。结果:模型组较对照组SOD活性降低,分别为(75.10±5.14)和(101.81±13.21)U/mL,F=5.7,P=0.00;MDA含量升高,分别为(13.60±2.88)和(5.28±3.14)nmol/mg,F=7.31,P=0.00;血浆LDH升高,分别为(5.27±0.58)×103和(2.23±0.47)×103 U/L,F=23.7,P=0.00;cTnI升高,分别为(483.38±52.07)和(264.16±52.07)ρg/mL,F=20.13,P=0.00;心肌细胞病理评分升高,分别为2.70±0.20和0,F=8.65,P=0.00;凋亡指数明显升高,分别为(66.54±3.46)%和(1.55±0.74)%,F=126.86,P=0.00。而加用右丙亚胺各组均较模型组提高SOD活性,降低MDA、血浆LDH及cTnI含量,减少心肌病理评分及心肌细胞凋亡指数,P<0.01或P<0.05。结论:右丙亚胺对表柔比星诱导的大鼠心肌损伤有保护作用,其机制可能与减少氧自由基的产生、降低脂质过氧化物含量以及调节心肌细胞凋亡机制有关。

OBJECTIVE：To study the intervent function of different doses of dexrazoxane on myocardial injury induced by epirubicin in rats and its mechanism.METHODS：Thirty-five SD rats were randomly divided into five groups,each of seven.The rats in control group were given bilaterally intraperitoneal injection of saline 5mL/kg,the interval time of30min,every other day,4times（7d）;In model group the rats were given intraperitoneal injection epirubicin 4.5mg/kg every other day,4times（7d）,injection table dexrazoxane 30min before epirubicin in other area intraperitoneal injection of saline 5mL/kg;In Epirubicin and low,medium and high dose dexrazoxane group the rats were given intraperitoneal injection of epirubicin 4.5mg/kg,every other day,4times（7d）,The dexrazoxane was injected 30min before epirubicin injection in another area intraperitoneally 45,67.5,90mg/kg,every other day,4times（7d）.The biochemical markers of myocardial tissue of rats in each group were detected,which included a trace of myocardial tissue malondialdehyde（MDA）content and total superoxide dismutase（T-SOD）activity,plasma lactate dehydrogenase（LDH）and troponin I（cTnI）levels,and observe myocardial pathological changes and cardiomyocyte apoptosis.RESULTS：The SOD activity was significantly lower in model group（75.10±5.14）U/mL than that of the control group（101.81±13.21）U/mL,（F=5.7,P=0.00）,MDA content was increased,（13.60±2.88）nmol/mg vs（5.28±3.14）nmol/mg,（F=7.31,P=0.00）.Plasma LDH[（5.27±0.58）×103 U/Lvs（2.23±0.47）×103 U/L,F=23.7,P=0.00]and cTnI content[（483.38±52.07）ρg/mL vs（264.16±52.07）ρg/mL,F=20.13,P=0.00],myocardial cell pathology score（2.70±0.20 vs 0,F=8.65,P=0.00）and apoptotic index[（66.54±3.46）%vs（1.55± 0.74）%,F=126.86,P=0.00]were significantly higher in epirubicin model group than that in the control group（P0.01）.SOD activity was higher,MDA,plasma LDH and cTnI content were lower in Each dexrazoxane group than that in epirubicin model group,that reduced myocardial pathology score and myocyte apoptosis index（P0.01or P0.05）.CONCLUSION：Dexrazoxane has a protective effect to myocardial injury induced by epirubicinin in rats and the mechanism may be to regulate myocardial apoptosis mechanism and reduce the generation of oxygen free radicals and lipid peroxide content.