Celecoxib对糖尿病大鼠缺血再灌注脑组织NF-κB和COX-2表达的影响

Effects of celecoxib on the expression of NF-κB and COX-2 in diabetic rats with focal cerebral ischemia-reperfusion

目的探讨celecoxib对糖尿病大鼠脑缺血再灌注后脑组织中NF-κB和COX-2表达的影响。方法采用SD大鼠腹腔注射链脲佐菌素(STZ)和线栓法制作糖尿病大鼠大脑中动脉缺血再灌注模型。大鼠分为假手术组(S组)、脑缺血再灌注生理盐水组(NS组)、celecoxib低剂量组(LCIR组)和高剂量组(HCIR组),分别于缺血后30min给予生理盐水或celecoxib溶液灌胃,再灌注后6、12、24、48h将大鼠断头取脑,免疫组化法检测脑组织中NF-κB和COX-2的表达。并对大鼠进行神经功能缺损评分。结果 NS组、LCIR组、HCIR组大鼠神经功能缺损评分有显著差异(P<0.05);NS组、LCIR组、HCIR组阳性细胞主要表达于缺血周边区神经元中,较S组表达明显增强(P<0.05),LCIR组、HCIR组阳性细胞表达率较NS组减少(P<0.05),LCIR组、HCIR组之间未见明显差异(P>0.05),每组不同时间点之间阳性细胞表达率有明显差异(P<0.05)。结论 celecoxib可能通过抑制糖尿病大鼠脑缺血-再灌注后脑组织中NF-κB和COX-2的表达,减轻神经功能缺损,从而发挥脑保护作用。

Objective To investigate the effects of eeleeoxib on the expression of NF-κB and COX-2 in diabetic rats with focal cerebral isehemic reperfusion. Methods Diabetes model was made by intraperitoneal injection of streptozotoein （STZ） and cerebral isehemia reperfusion（IR） model was developed by Longa suture occluded method in middle cerebral artery of diabetic rats. The rats were divided into sham operation group （S group） , cerebral isehemia-reporfusion in normal saline group （ NS group）, eeleeoxib low-close group （ LCIR group） and high-dose group （ HCIR group）. After 30 minutes following isehemia, rats were respectively given normal saline or eeleeoxib solution. Respectively at 6h, 12h, 24h and 48h after reperfusion,the rats were decapitated and the brains were collected. The dynamic expression of NF-κB and COX-2 in the ipsilateral cortex was detected with immunohistochemistry and the neurological deficit scores were done. Results The neurological deficit scores showed significant difference among the NS, LCIR and HCIR group （P 〈 0.05 ）. In the cortex of the rats of NS, LCIR and HCIR groups, expression of positive cells was mainly surrounding the ischemic neurons, and the numbers of positive ceils were more than that of S group （ P 〈 0.05 ）. The rate of positive staining in LCIR group and HCIR group was highly reduced than that of NS group （ P 〈 0.05 ） , while no significant difference was detected between LCIR group and HCIR group（ P 〉 0.05 ）. At 6h, 12h,24h and 48h after reperfusion（ the four sub-groups） , the percentage of positive labeled cells is significant different （ P 〈 0.05 ）. Conclusion Celecoxib probably plays an important role in cerebral protection by inhibiting the expression of COX-2 and NF-κB in diabetic rats with cerebral ischemia-reperfusion.