【摘要】 目的观察不同剂量过氧化物酶体增殖物激活受体γ(PPARγ)激动剂马来罗格列酮对脑缺血再灌注大鼠Fractalkine(FKN)表达的影响,探讨PPARγ激动剂对脑缺血再灌注损伤的作用和机制。方法取健康雄性Sprague-Dawley大鼠60只,将其随机分入假手术组、缺血再灌注模型组(模型组)、马来酸罗格列酮0.5mg/kg组(小剂量组)、马来酸罗格列酮2mg/kg组(中剂量组)、马来罗格列酮5mg/kg组(大剂量组),每组12只。假手术组和模型组以相同体积的0.9%氯化钠溶液灌胃,分别于缺血2h、再灌注24h后处死大鼠。马来酸罗格列酮小剂量组、中剂量组、大剂量组大鼠于缺血即刻和缺血2h后经胃管分别灌入马来酸罗格列酮0.5、2和5mg/kg。参考Longa线栓法制备大脑中动脉栓塞模型。分别采用2,3,5-氯化三苯基四氮唑(TTC)染色法观察脑梗死体积,H-E染色观察缺血周边区病理学变化,免疫组织化学法检测FKN阳性细胞表达情况。结果中剂量组和大剂量组的Longa评分均显著低于模型组(P值均<0.05),脑梗死体积均显著小于模型组(P值均<0.05),平均光密度(AOD)值均显著低于模型组(P值均<0.05)。小剂量组和模型组大鼠的AOD值均显著高于假手术组(P值均<0.01)。结论马来酸罗格列酮对脑缺血再灌注损伤的保护作用可能与下调FKN表达有关,且以大、中剂量的效果较好。更多还原

【Abstract】 Objective To investigate the effect of rosiglitazone maleate,an excitomotor of peroxisomeproliferator activated receptor gamma(PPARγ),on the expression of Fractalkine(FKN)after focal cerebral ischemia-reperfusion in rats.Methods Sixty healthy male Sprague-Dawley rats were randomly divided into five groups(n=12):sham operation group,NS control group,low-dose rosiglitazone group(0.5mg/kg),moderatedose rosiglitazone group(2mg/kg)and high-dose rosiglitazone group(5mg/kg).Rosiglitazone maleate(0.5,2and 5mg/kg)was given by stomach catheter immediately and 2hafter middle cerebral artery occlusion in three rosiglitazone groups,respectively.Isometric 0.9% sodium chloride solution was perfused in sham operation group and NS control group.The rats were sacrificed at 2hafter brain ischemia and 24 hafter reperfusion,respectively.Focal cerebral ischemia was induced by the intraluminal suture for middle cerebral artery occlusion.Cerebral infarction area was measured by 2,3,5-triphenyl four azole nitrogen chloride(TTC)staining.The pathologic changes were observed by hematoxylin and eosin(H-E)staining.The protein expression of FKN was measured by immunohistochemical method.Results The Longa rating of moderate and high dose rosiglitazone groups were significantly lower than that of NS control group(both P<0.05).Cerebral infarction volume and AOD value of moderate and high dose rosiglitazone groups were significantly less than that of NS control group(both P<0.05).AOD values of low dose rosiglitazone group and NS control group were significantly higher than that of sham operation group(both P<0.01).Conclusion Rosiglitazone can ameliorate the brain ischemic injury after middle cerebral artery occlusion by decreasing the expression of FKN.Moderate and high doses are more effective than low dose.更多还原