兔心脏缺血再灌注损伤后重组水蛭素的保护作用及其机制

背景重组水蛭素能否通过抑制白细胞浸润来拮抗心肌缺血/再灌注(ischemia/reperfusion,IR)损伤,从而起到对心肌的保护作用?目的观察重组水蛭素对缺血心肌内白细胞浸润的影响,进一步探讨重组水蛭素对心肌保护的作用机制.设计随机对照的实验研究.地点、材料和干预本实验在第四军医大学唐都医院心血管病实验室完成.选取24只日本大耳白兔随机分为2组,每组12只.IR组;心脏左冠状动脉前降支IR动物模型,缺血45 min、再灌注120 min,再灌注前后静脉应用生理盐水;重组水蛭素组缺血45 min、再灌注120 min,再灌注前15 min静注重组水蛭素(1 mg/kg),再灌注时继以持续静滴重组水蛭素1 mg/(kg·h)]120 min.主要观察指标心肌梗死范围及缺血心肌内白细胞浸润的变化.结果重组水蛭素组的心肌梗死范围为(11.7±2.4)%,与缺血再灌注组的(21.2±5.3)%比较,梗死范围明显缩小(t=7.436,P＜0.01).缺血再灌注组的髓过氧化物酶(myeloperoxidase,MPO)活性为(56.01±3.83)nkat/g,重组水蛭素组(35.51±1.67)nkat/g.重组水蛭素组缺血心肌内白细胞聚集较缺血再灌注组显著减少(t=3.935,P＜0.05).结论重组水蛭素能够抑制再灌注期缺血心肌内白细胞浸润,拮抗心肌IR损伤.

Protection of recombinant hirudin against myocardial ischemia-reperfusion injury in rabbits and its mechanism

BACKGROUND: It is not very clear that recombinant hirudin(r-hirudin)can inhibit the ueutrophil infiltration against myocardial ischemia-reperfusion(IR) injury.OBJECTIVE: To observe the effect of r-hirudin on the accumulation of neutrophils in ischemic cardiac tissues and investigate its protective mechanism against myocardial IR injury in rabbits.DESIGN: A randomly controlled experimental study.SETTING, PARTICIPANTS and INTERVENTIONS: The experiment was performed at the institute of cardiovascular disease research of Tangdu Hospital, Fourth Military Medical University of Chinese PLA. A total of 24 rabbits were randomly divided into ischemia-reperfusion (IR) group ( n = 12) and r-hirudin group ( n = 12). In the IR group the left anterior descending coronary artery was occluded for 45 minutes followed by 120 minutes reperfusion, and saline was infused before and during reperfusion. In the r-hirudin group, the operation on rabbits was the same as IR group and r-hirudin treatment began with the intravenous administration of 1 mg/kg 15 minutes before reperfusion,following reperfusion.MAIN OUTCOME MEASURES: Changes of the infarct size and the neutrophil infiltration in ischemic cardiac tissues were observed.RESULTS: R-hirudin resulted in a significant reduction in the infarct size with respect to rabbits in IR group (11.7±2.4)% vs (21.2±5.3%)]( t = 7.436, P ＜ 0.01 ). The MPO activity was (56.01 ± 3.83)nkat/g and (35.51 ± 1.67) nkat/g respectively in the r-hirudin and IR groups. In the r-hirudin group, the neutrophil infiltration in ischemie cardiac tissues was significantly decreased in comparison with that in the IR group ( t = 3.935,P ＜0.05).CONCLUSION: R-hirudin has the cardioprotective action against myocardial IR injury by inhibiting neutrophil infiltration in ischemic myocardial tissues.