Celecoxib对糖尿病大鼠缺血再灌注脑组织NF-κB和ICAM-1表达的影响  

Effects of celecoxib on the expression of NF-κB and ICAM-1 in diabetic rats with focal cerebral ischemia-reperfusion

作　　者：祁学章[1] 范瑞明[2] 杨丽[2] 余昌胤[2] 

机构地区：[1]湖北省鄂州市中心医院神经内科,436000 [2]遵义医学院附属医院神经内科

出　　处：《卒中与神经疾病》2013年第6期327-330,335,共5页Stroke and Nervous Diseases

基　　金：贵州省卫生厅资助项目(编号D-287)

摘　　要：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ICAM-1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ICAM-1的表达水平。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NF-κB阳性细胞及ICAM-1阳性微血管主要表达于缺血周边区,较S组表达明显增强(P<0.05),LCIR组、HCIR组NF-κB阳性细胞表达率及ICAM-1阳性微血管数较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NF-κB阳性细胞表达率有明显差异(P<0.05)以及它们之间的ICAM-1阳性微血管数也有明显差异(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ICAM-1的表达而减轻神经功能缺损,从而发挥脑保护作用。Objective To investigate the effects of celecoxib on the expression of NF-nB and ICAM-1 in diabetic rats with focal cerebral ischemic reperfusion. Methods Diabetes model was made by intraperitoneal in- jection of streptozotocin （STZ） and cerebral ischemia reperfusion （IR） which was developed by longe suture occluded method in middle cerebra[ artery of diabetic rats. The rats were divided into sham operation group（S group）, cerebral ischemia-reperfusion in normal saline group （NS group）, celecoxib low-dose group （LCIR group） and high-dose group （HCIR group）. After 30 minutes following ischemia, rats were respectively given normal saline or celecoxib solution. Respectively at 6 h, 12 h,24 h,48 h after reperfusion, the rats were decapi- tated and the brains were collected. The dynamic expression of NF-kB and ICAM-1 in the ipsilateral cortex was detected by immunohistochemistry and the neurological deficit scores were done. Results The neurological def- icit scores are significant difference among the NS, LCIR and HCIR group（P〈0. 05）. In the rats cortex of NS, LCIR and HCIR groups, expression of NF-kb and ICAM-1 are mainly around the ischemic issue, and the number of NF-kb positive cells and blood capillary indicated by ICAM-1 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. （15） ,while no significant difference was detected between LCIR group and HCIR group （P〉0. 05）. At 6 h, 12 h ,24 h,and 48 h after reperfusio（the four sub-groups）, the percentage of positive labeled cells is sig- nificant different （P〈0. 05）. The expression of ICAM-1 and NF-kB were obvious relevant to each other at the same time point in ischemic brain tissue. Conclusions Celecoxib probably plays an important role in cerebral protection by inhibiting the expression of ICAM-1 and NF-kB in diabetic rats with cerebral ischemia-reperfu-sion.

关 键 词：CELECOXIB 糖尿病 脑缺血再灌注 核因子 细胞间粘附因子 

分 类 号：R587.1[医药卫生—内分泌] R743[医药卫生—内科学]