促红细胞生成素对婴幼儿先天性心脏病围术期心肌保护的作用及机制

Erythropoietin pretreatment for myocardial protection in perioperative period of infant congenital heart disease operation

目的 探讨促红细胞生成素（erythropoietin,EPO）预处理对婴幼儿先天性心脏病围术期心肌的保护作用及其可能的机制.方法 选取中国医科大学附属盛京医院心脏外科2014年4月至2017年1月进行体外循环心内直视手术的80例非紫绀型先天性心脏病患儿.采用区组随机的方法将患儿分为A、B、C三组.A组患儿术前12 h皮下注射EPO 150 IU/kg,B组患儿术前12 h皮下注射EPO 300 IU/kg,C组（对照组）不注射EPO,其他处理同A、B两组.所有患儿分别于入院后及手术后24 h、48 h、72 h检测心肌酶学指标.手术结束后取右心耳组织,分别用Real-time PCR和Western blot方法检测HSP70和ERK1/2 mRNA及蛋白水平的表达变化.结果 A组和B组在手术结束后各时间点,心肌酶学指标明显低于对照组,差异有统计学意义（P〈0.05）;A组水平较B组低（P〈0.05）.Real-time PCR及Western blot检测结果显示,与对照组相比,A组、B组HSP70、ERK1/2 mRNA及蛋白表达量均显著升高（P〈0.05）;A组HSP70、ERK1/2 mRNA及蛋白显著高于B组（P〈0.05）.结论 EPO预处理对于体外循环术中的心肌具有一定的保护作用.EPO可能通过上调HSP70及ERK1/2的表达诱导心肌的内源性保护作用,并且150 IU/kg EPO对心肌保护的作用效果更显著.

Objective To study the effect of erythropoietin（ EPO） pretreatment on myocardial pro-tection in perioperative period of infant congenital heart disease operation and explore its underlying mecha-nism. Methods All the 80 patients who were suffered from non-cyanotic congenital heart disease undergone cardiopulmonary bypass in open heart operation were selected from Shengjing Hospital of China Medical Uni-versity cardiac surgery ward from April 2014 to January 2017. The patients were randomly divided into A,B, C three groups according to blocked randomization method. Group A patients were treated with subcutaneous injection of EPO 150 IU/kg 12 hours before operation,group B patients were treated with subcutaneous injec-tion of EPO 300 IU/kg 12 hours before operation,patients in group C（ control group） had no treatment. All patients were detected myocardial zymetology after admission to hospital as well as 24 h,48 h,72 h after oper-ation. HSP70,ERK1/2 mRNA and protein expression in right auricle were detected by qRT-PCR and Western blot method,respectively. Results At each time point after operation,myocardial zymetology were signifi-cantly lower in group A and B compared with group C,the index of myocardial zymetology in group A were lower than that in group B（P〈0. 05）. The expressions of HSP70,ERK1/2 mRNA and protein were signifi-cantly up-regulated in group A and B compared to the control group（P〈0. 05）. The expressions of HSP70, ERK1/2 mRNA and protein in group A were significantly higher than those in group B （ P 〈 0. 05 ） . Conclusion EPO pretreatment has a positive effect on the myocardial protection during cardiopulmonary bypass. EPO may act a role of endogenous myocardial protection through up-regulation of the expressions of HSP70 and ERK1/2. The dosage of 150 IU/kg EPO is more significant on the effect of myocardial protection.