目的探讨局灶脑缺血再灌注大鼠不同时间点大脑皮质炎症反应及IKK-NBD多肽干预对抗炎症反应的机制。方法采用线栓法制备Spragne-Dawley(SD)大鼠局灶脑缺血再灌注模型。将大鼠分为假手术组、模型组及IKK-NBD组,再下设再灌注1 d和7 d 2个时相点。IKK-NBD组通过侧脑室定位定量注入4μL IKK-NBD。对各组进行Zea-Longa神经功能评分,HE染色观察病理变化,Western blot与荧光定量PT-PCR分别检测缺血皮质区c-rel蛋白和IκappaBα(IκBα)mRNA表达,ELISA检测缺血区炎症因子IL-1β和IL-10的含量。结果①再灌注1、7 d时,IKK-NBD对模型大鼠行为学改善明显;②再灌注1、7 d时,模型组病理改变较IKK-NBD组明显;③胞核c-rel蛋白:再灌注1、7 d时,模型组均高于假手术组(P<0.05);再灌注1 d时,IKK-NBD组高于假手术组(P<0.05);再灌注1、7 d时,IKK-NBD组低于模型组(P<0.05,P<0.01);随着时间延长模型组和IKK-NBD组均降低(P<0.01);④IκBαmRNA:再灌注1、7 d时,模型组和IKK-NBD组均高于假手术组(P<0.05),7 d较1 d回落;再灌注1 d时,IKK-NBD组高于模型组(P<0.01);⑤IL-1β:再灌注1、7 d时,模型组与IKK-NBD组均明显高于假手术组(P<0.01),浓度随时间降低;再灌注1 d时,IKK-NBD组较模型组减少(P<0.01);IL-10:再灌注1、7 d时,模型组与IKK-NBD组均明显高于假手术组(P<0.01),浓度随时间降低;再灌注1、7 d时,IKK-NBD组均高于模型组(P<0.01)。结论 IKK-NBD在局灶脑缺血再灌注损伤后早期可以通过上调IκBα限制c-rel入核,下调IL-1β,上调IL-10而减轻再灌注后炎症损伤;而脑缺血再灌注恢复期,少量c-rel可上调IL-10起到抗炎作用。 Objective To investigate the inflammatory response of cerebral cortex at different time points after focal cerebral ischemia-reperfusion in rats and the mechanism of IKK-NBD polypeptide intervention on anti-inflammation. Methods Sprague-Dawley (SD) rat models of focal cerebral ischemia-reperfusion were established by thread occlusion. The rats were divided into sham-operation group, model group and IKK-NBD group. Then two time points of reperfusion were established at 1 and 7 days after reperfusion. The IKK-NBD group was injected with 4 μL IKK-NBD by lateral ventricle positioning. The neurological deficits of Zea-Longa were observed in each group. The pathological changes were observed by HE staining. The expressions of c-rel protein and IκBαα mRNA in ischemic cortex were detected by Western blot and fluorescent quantitative PT-PCR. IL-1β and IL-10 content. Results ① At 1 and 7 days after reperfusion, IKK-NBD significantly improved the behavior of model rats. ② At 1 and 7 days after reperfusion, the pathological changes in model group were more obvious than those in IKK-NBD group. ③ The nuclear c-rel protein: At 1 and 7 days after reperfusion, the model group was higher than the sham-operated group (P <0.05). At 1 day after reperfusion, the IKK-NBD group was higher than the sham-operated group (P <0.05) (P <0.05, P <0.01). The expression of IκBαmRNA in IKK-NBD group was lower than that in IKK-NBD group (P <0.01) And IKK-NBD group were significantly higher than those in sham-operation group (P <0.05), and the levels of IKK-NBD in IKK-NBD group were higher than those in model group (P <0.01) At 1 and 7 days, the concentrations of IKK-NBD in model group and IKK-NBD group were significantly lower than those in sham operation group (P <0.01) ; The level of IL-10 in the IKK-NBD group was significantly higher than that in the sham group (P <0.01) at 1 and 7 days after reperfusion, Were higher than the model group (P <0.01). Conclusion IKK-NBD can reduce the expression of IL-1β, upregulate IL-10 and reduce the inflammatory injury after focal cerebral ischemia-reperfusion injury by inducing IκBα upregulation in the early stage after focal cerebral ischemia-reperfusion injury. A small amount of c-rel can up-regulate IL-10 and play an anti-inflammatory role.