吡格列酮对脑缺血再灌注损伤大鼠环氧化酶2表达及脑保护作用机制研究

摘要

目的 探讨吡格列酮对脑缺血再灌注大鼠的脑保护作用及机制.方法 80只雄性SD大鼠完全随机分为假手术组、生理盐水组(NSP组)、小剂量吡格列酮干预组(LDPP组,吡格列酮:10 mg/kg)、大剂量吡格列酮干预组(HDPP组,吡格列酮:15 mg/kg)各20只.采用线栓法制作大鼠局灶性脑缺血再灌注模型.缺血2 h再灌注22 h后观察大鼠神经功能评分,测量脑梗死体积,用免疫组化法观察大鼠额顶部皮质环氧化酶2(COX-2)表达.结果 与NSP组比较,应用吡格列酮干预组的LDPP组和HDPP组大鼠的神经功能评分明显降低、脑梗死体积缩小[神经功能评分:(1.8±0.6)分、(1.5±0.4)分比(2.7±0.8)分,均P＜0.05;脑梗死体积比:(23.4±8.8)%、(15.3±7.1)%比(37.4±9.4)%;均P＜0.01].NSP组、LDPP组和HDPP组额顶叶皮质COX-2表达分别为78.7±6.7、65.6±6.1、48.7±5.1,与假手术组(脑组织中未见COX-2阳性表达)比较,NSP组额顶叶皮质COX-2表达明显增加.与NSP组比较,LDPP组和HDPP组的COX-2表达均明显减少(均P＜0.05),尤其以HDPP组更明显.结论 吡格列酮对大鼠局灶性脑缺血再灌注损伤有防护作用,以大剂量组为优,其保护机制与其抑制脑组织COX-2表达、减轻脑组织炎症反应有关.%Objective To investigate the effect of different dose of pioglitazone on the expression of cyclooxygenase-2(COX-2) in focal cerebral ischemia-reperfusion injury in rats and to study the protective effect and the mechanism of pioglitazone. Methods Eighty adult male SD rats were randomly divided into four groups: sham operated group, normal sodium pretreated group(NSP group), low-dose pioglitazone pretreated group(LDPP group,10 mg/kg) and high-dose pioglitazone pretreated group(HDPP group, 15 mg/kg). Animal models of 2 h middle cerebral artery occlusion followed by 22 h reperfusion (MCAO/R) were made by suture-occluded method. After MCAO/R, we evaluated the neurological score, measured the volume of cerebral infarction, investigated the expression of COX-2 with immunohistochemistry. Results Compared with NSP group, rats in pioglitazone pretreated group(LDPP group and HDPP group), especially in HDPP group, significantly presented lower neurological score and smaller cerebral infarction volume(P ＜ 0. 01). The expression of COX-2 of fronto-parietal lobe in NSP group were significantly increased while compared with sham operated group(P ＜ 0.05). Compared with NSP group, the expression of COX-2 in pioglitazone pretreated group, especially in HDPP group, was significantly decreased (all P＜0.05). Conclusions Pioglitazone has protective effect on focal cerebral ischemia-reperfusion injury in rats,especially in HDPP group. The protective mechanism of pioglitazone is probably related to the decreased expression of COX-2 and the improvement of inflammatory reaction in brain tissue.