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(英文)

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

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45min、再灌注120min,再灌注前后静脉应用生理盐水;重组水蛭素组:缺血45min、再灌注120min,再灌注前15min静注重组水蛭素(1mg/kg),再灌注时继以持续静滴重组水蛭素犤1mg/(kg·h)犦120min。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。

BACKGROUND:It is not very clear that recombinant hirudin(r-hirudin) can inhib it the neutrophil infiltration against myocardial ischemia-reperfusion (IR) inj ury. OBJECTIVE: To observe the effect of r-hirudin on the accumulation of neutroph ils 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 in stitute of cardiovascular disease research of Tangdu Hospital, Fourth Military M edical University of Chinese PLA. A total of 24 rabbits were randomly divided in to 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 re perfusion. 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, and continued with an intravenous infusion of 1 mg/(kg·h) for 120 minutes following reperfusion. MAIN OUTCOME MEASURES: Changes of the infarct size and the neutrophil infiltra tion in ischemic cardiac tissues were observed. RESULTS: R-hirudin resulted in a significant reduction in the infarct size wi th 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 respective ly in the r-hirudin and IR groups. In the r-hirudin group, the neutrophil infi ltration in ischemic cardiac tissues was significantly decreased in comparison w ith that in the IR group (t=3.935,P< 0.05). CONCLUSION: R-hirudin has the cardioprotective action against myocardial IR i njury by inhibiting neutrophil infiltration in ischemic myocardial tissues.