E-选择素介导大鼠脑缺血再灌注后继发炎症损伤实验干预.docVIP

E-选择素介导大鼠脑缺血再灌注后继发炎症损伤实验干预 　 作者：盛文利， 李锐， 许晓伟， 王彦莉， 黄如训， 曾进胜 【摘要】 　　【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2 h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8 h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。 【关键词】 脑梗死； E-选择素； 左旋精氨酸（L-arg）； 一氧化氮； 易卒中型肾血管性高血压大鼠(RHRSP) Abstract:【Objective】 To evaluate whether L-arginine 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=48) or 0.9% saline vehicle(n=72). Nitrite(NO2-) ，nitrate(NO3-) and myeloperoxidase activity of ischemic brain tissue were detected, and the expression of E-selectin was measured by immunofluoresecent staining and RT-PCR. 【Results】 At 0 h, 4 h and 8 h later of reperfusion, Nitrite(NO2-) and nitrate(NO3-) detected in the L-arginine of MCAO group（52±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. Key words: cerebral infarction； E-selectin； L-arginine（L-arg）； nitric oxide (NO)； stroke-prone renovascular hypertensive r