E-选择素介导的大鼠脑缺血再灌注后继发炎症损伤的实验干预

Experimental Intervention of Secondary Inflammation Injuries Induced by E-selectin During Cerebral Ischemia/reperfusion in Rats

【目的】通过在大鼠脑缺血后再灌注期间使用左旋精氨酸干预黏附分子E-选择素的表达从而减轻炎症损伤。【方法】先后复制易卒中型肾血管性高血压大鼠(RHRSP)模型和右侧大脑中动脉缺血2h再灌注(MCAO/R)线栓模型(n=192),并设立MCAO假手术组(n=48)。入选MCAO大鼠随机分为3个组,分别于缺血早期给予左旋精氨酸(n=72)、右旋精氨酸(n=48)和等体积生理盐水(n=72)。测定缺血侧脑组织NO代谢物含量、MPO活性、间接免疫荧光染色和RT-PCR方法检测E-选择素表达。【结果】左旋精氨酸组缺血后至再灌注0、4和8h后NO代谢物含量(52±12、81±34、131±27)高于相应时间段的盐水组(43±14、40±17、105±39)和右旋精氨酸组(38±13、34±16、109±29)。左旋精氨酸组大鼠缺血及再灌注早期E-选择素表达及MPO活性低于右旋精氨酸组和盐水组。【结论】大鼠脑缺血早期使用左旋精氨酸可以增加缺血区域NO含量,减少缺血再灌注早期E-选择素的表达和中性粒细胞的浸润。

[Objective] To evaluate whether L-arginlne could decrease E-selelctin expression and reduce inflammation damage during focal cerebral ischemia and reperfusion of the rat. [Methods] Middle cerebral artery occlusion and reperfusion （MCAO/R） model according Longa＇s method and sham operation model were made in the stroke-prone renovascular hypertensive rats（RHRSP）. MCAO/R rats were randomly divided into 3 groups receiving L- argnine（n=72）, D-arginine （n=8） or 0.9% saline vehicle（n=72）. Nitrite（NO^2-） ,nitrate（NO^3-） and myeloperoxidase activity of ischemic brain tissue were detected, and the expression of E-selectin was measured by immunofluoresecent staining and RT-PCIL [Results] At 0 h, 4 h and 8 h later of rvperfusion, Nitrite（NO2-） and nitrate（NO3-） detected in the L-arginine of MCAO group（S2±12, 81±34, 131±27） were higher than those in saline（43±14, 40±17, 105±39） or D-arginine（38±13, 34±16, 109±29） of MCAO groups. During the earlier time of ischemia/reperfusin, the expression of E-selectin ,and myeloperoxidase activity in the groups of MCAO with L-arginine infusions , downregulated in contrast to the other two MCAO groups. [ConclusionS] L-arginine administered in the early stage of ischemia can upregulate the NO, which can inhibit the expression of E-selectin.