p55TNFR选择性淋巴毒素对大鼠缺血再灌注后心脏损伤的保护作用

Protection against myocardial ischemia-reperfusion injury in rats by a novel selective lymphotoxin binding p55TNFR

目的 研究p55TNFR选择性淋巴毒素对缺血-再灌注后心脏损伤的保护作用,并探讨其作用机制.方法 SD大鼠40只随机（随机数字法）分为4组,A组为假手术组,B组为大鼠心脏缺血-再灌注（I/R）模型组,C组为25 μg/（kg·d）野生型淋巴毒素（rhLTα）治疗组,D组为25 μg/ （kg·d）p55TNFR选择性淋巴毒素（rhLTα-Q107E）治疗组.各组在制备I/R模型后微量泵持续24h静脉滴注生理盐水或治疗药物,24h后检测血浆中心肌酶谱（AST、LDH、CK）、氧化/抗氧化指标（SOD、MDA、GSH-Px）,硝基蓝四唑染色计算心肌梗死面积.结果 大鼠心脏缺血-再灌注（I/R）模型心肌梗死面积显著增高,心肌酶谱指标、MDA较假手术组明显升高（P＜0.05）,SOD和GSH-Px则明显降低（P＜0.05）.rhLTα-Q107E治疗组可逆转心肌缺血-再灌注后心肌酶谱指标、MDA的升高及SOD和GSH-Px的下降（P＜0.05）,而野生型rhLTα治疗组的作用不明显（P＞0.05）.结论 p5STNFR选择性淋巴毒素对大鼠心脏缺血-再灌注后的急性心脏损伤具有保护作用,其机制可能通过直接清除氧自由基、增加内源性抗氧化酶系统的活力而发挥保护作用.

Objective To investigate the effect of a novel lymphotoxin with selectively binding to p55 tumor necrosis factor receptor （p55TNFR） on myocardial ischemia-reperfusion injury in rats in order to explore the mechanism.Methods A total of 40 SD rats were randomly （random number） assigned into four groups （n =10 in each）,namely sham operation group （group A）,I/R group （group B）,wild type rhLTα treatment group （group C）,and p55TNFR selective rhLTα （rhLTα-Q107E） treatment group （group D）.After I/R model rats were established,various therapeutic agents or saline were given by continuous intravenous infusion for 24 h via a micropump.After 24 hours of treatment,serum myocardial zymogram,such as aspartate aminotransferase （AST）,lactate dehydrogenase （LDH） and creatine kinase （CK）,as well as superoxide dismutase （SOD）,malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） activities were determined.Myocardial infarction size （MIS） was measured by nitro blue tetrazolium chloride （NBT） staining.Results Compared to sham operation group,MIS,AST,LDH,CK,MDA were increased,while the activities of SOD and GSH-Px were decreased.However,all the effects were significantly reversed by treatment with rhLTα-Q107E （P 〈 0.05） but not rhLTα （P 〉 0.05）.Conclusions The rhLTα-Q107E plays a role in the protection against myocardial ischemia-reperfusion injury in rats by the mechanism of scavenging oxygen free radicals and increasing the activity of endogenous antioxidant system.