促红细胞生成素和氨甲酰化衍生物对慢性心力衰竭大鼠抗心肌细胞凋亡及机制的研究

摘要

目的 探究促红细胞生成素(EPO)及氨甲酰化抗慢性心力衰竭大鼠心肌细胞凋亡的保护作用及其可能的机制.方法 将39只健康雄性SD大鼠随机分为对照组、EPO组及CEPO组.所有大鼠均采用腹腔注射异丙肾上腺素法建立大鼠心力衰竭模型.干预4周后,检测3组大鼠血流动力学指标变化,血清中iNOS、SOD水平及心肌细胞凋亡情况并计算凋亡指数(AI)和心肌细胞凋亡率.结果 与对照组比较,EPO组与CEPO组LVSP、±dp/dtmax均显著提高,而HR及LVEDP显著下降,差异有统计学意义(P<0噰.05);EPO组与CEPO组间血流动力学指标变化差异有统计学意义(P<00.5);EPO组与CEPO组SOD水平与对照组比较显著上升(P<0.05),而iNOS水平显著下降(P<0.05);EPO组与CEPO组间iNOS、SOD水平差异有统计学意义(P<0.05);3组大鼠心肌细胞凋亡指数以对照组最高(36.53%),EPO组次之(23.73%),CEPO组最低(19.64%),心肌细胞凋亡指数差异有统计学意义(P<0.05);3组大鼠不同时间点心肌细胞凋亡率按照对照组、EPO组及CEPO组的顺序依次降低,差异有统计学意义(P<0.05).结论 EPO及CEPO可有效改善CHF大鼠的心功能,抑制心肌细胞凋亡CEPO的功效要优于EPO,其发生机制可能与机体内血清中的iNOS及SOD水平有关.%Objective To investigate the protective effects and possible mechanism of erythropoietin ( EPO ) and carbamoylation on cardiomyocytes apoptosis of rats with chronic heart failure (CHF).Methods Thirty-nine healthy male SD rats were randomly divided into control group , EPO group and CEPO group .The animal models with heart failure were established by intraperitoneal injection with ISO-epinephrine in all the rats .After 4 -week intervention , the changes of hemodynamic parameters,the serum levels of iNOS and SOD as well as apoptotic index (AI) and apoptosis rate of myocardial cells were detected and calculated .Results As compared with those in control group , LVSP and ±dp/dtmax in EPO group and CEPO group were significantly increased ,however, HR and LVEDP were significantly decreased ( P <0.05).There were significant differences in hemodynamic parameters between EPO group and CEPO group ( P <0.05).As compared with those in control group, SOD levels in EPO group and CEPO group were significantly increased ( P <0.05),however, iNOS levels were significantly decreased ( P <0.05).There were significant differences in iNOS and SOD levels between EPO group and CEPO group ( P <0.05).Among the three groups,the AI in control group was the highest (36.53%),the next in order EPO group (237.3 %),which in CEPO group was the lowest (19.64%),there was a significant difference in AI among the three groups ( P <0.05).Moreover the decrease order of apoptosis rate in different time points was control group ,EPO group, CEPO ( P <0.05).Conclusion The EPO and CEPO can effectively improve the cardiac function of rats with CHF ,and the inhibition efficiency of CEPO is superior to that of CPO ,and its action mechanism may be related to the changes of serum levels of iNOS and SOD .