细胞穿透肽PEP-1介导血红素加氧酶-1对大鼠缺血心肌的转导及影响

目的:探讨细胞穿透肽PEP-1介导血红素加氧酶-1(HO-1)对大鼠心肌缺血再灌注损伤的影响。方法:制备融合蛋白PEP-1/HO-1,通过酶联免疫吸附法检测给予融合蛋白后各时间点血清HO-1水平,探讨动物实验给予融合蛋白的最佳时间点。健康雄性SD大鼠18只,体重220-280g,随机分为3组:正常对照组(C组,n=6)、缺血再灌注组(IR组,n=6)和PEP-1/HO-1处理+缺血再灌注组(HO组,n=6)。制备心肌缺血再灌注损伤模型,于再灌注结束后,测定血清肌酸激酶(CK)和乳酸脱氢酶(LDH)的活性及心肌梗死面积。结果:给予融合蛋白后,血清HO-1蛋白浓度在1h和3h达峰值。与C组比较,IR组血清CK和LDH活性升高,心肌梗死面积增加(P<0.05);与IR组比较,HO组血清CK和LDH活性降低,心肌梗死面积减少(P<0.05)。结论:细胞穿透肽PEP-1介导的HO-1对大鼠心肌缺血再灌注损伤具有保护作用。

Transduction and Effect of Heme Oxygenase-1 Mediated by Cell Penetrating Peptide PEP-1 on Myocardial Ischemia in Rats

Objective: To investigate the protective effects of heme oxygenase-1(HO-1) mediated by cell penetrating peptide PEP-1 on myocardial ischemia/reperfusion(I/R) injury in rats.Methods: Fusion protein PEP-1/HO-1 was prepared.After intravenous injection of fusion protein PEP-1/HO-1,serum HO-1 was determined at different time points by ELISA to explore the best time point of injection.Eighteen male SD rats weighing 220-280 g were randomly and equally divided into three groups: control group,I/R group,and PEP-1/HO-1 + I/R group(HO group).The left anterior descending coronary artery was ligated for 30 minutes and loosed for 120 minutes to establish the model of myocardial I/R injury.After 120 minutes reperfusion,activities of serum creatine kinase(CK) and lactic dehydrogenase(LDH),and myocardial infarct size were determined.Results: HO-1 protein serum levels reached the peak level at the 1st and 3rd hours after the treatment of fusion protein PEP-1/HO-1.Compared with those respectively in control group,the activities of serum CK and LDH and myocardial infarct size increased in IR group versus those in control group,and decreased in HO group versus those in I/R group(all P<0.05).Conclusion: HO-1 mediated by cell penetrating peptide PEP-1 has the protective effect on myocardial I/R injury in rats.