Celecoxib对糖尿病大鼠缺血再灌注脑组织ICAM-1和MMP9表达及神经功能的影响

目的探讨celecoxib(塞来昔布)对糖尿病大鼠脑缺血再灌注后脑组织中ICAM-1和MMP9表达及神经功能的影响。方法将SD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)。采用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。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ICAM-1和MMP9的表达,并对大鼠进行神经功能缺损评分和死亡率的比较。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MMP9及ICAM-1阳性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MMP9及ICAM-1阳性血管数较NS组减少(P<0.05),LCIR组、HCIR组之间差异不明显(P>0.05),各组不同时间点之间MMP9及ICAM-1阳性血管数均有明显差异(P<0.05)。经Celecoxib干预后大鼠死亡率明显下降。结论 celecoxib可能通过抑制脑组织中MMP9和ICAM-1的表达而减轻糖尿病大鼠脑缺血-再灌注后神经功能的损伤而降低实验大鼠的死亡。

Effects of celecoxib on the expression of ICAM-1 and MMP9 in diabetic rats with focal cerebral ischemia-reperfusion

Objective To investigate the effects of celecoxib on the expression of ICAM-1 and MMP9 in diabetic rats with focal cerebral ischemic reperfusion and the change of neurologic function.Methods The SD 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).Diabetes model was made by intraperitoneal injection of streptozotocin(STZ)and cerebral ischemia reperfusion(IR)model was developed by thread embolism method in middle cerebral artery of diabetic rats.After 30 minutes following ischemia,rats were respectively given normal saline or celecoxib solution.Respectively at 6h,12h,24h and 48h after reperfusion,the rats were decapitated.The dynamic expression of ICAM-1 and MMP9 in the ipsilateral cortex was detected with immunohistochemistry,and the neurological deficit scores and comparison of mortality were done.Results The neurological deficit scores were 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 ICAM-1 and MMP9 were mainly around the ischemic issue,and the number of blood capillary indicated by ICAM-1 and MMP9 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 percentage of positive labeled cells is significantly different(P<0.05).Conclusion Celecoxib can inhibit the expression of ICAM-1 and MMP9 in diabetic rats with cerebral ischemia-reperfusion and reduce neurological damage.