目的了解缺血后处理(IP)对大鼠局灶性脑缺血再灌注时Toll样受体4(TLR4)和核因子-κB(NF-κB)表达的影响,探讨TLR4-NF-κB信号通路在脑IP中的作用。方法成年健康雄性SD大鼠110只,随机分为假手术组(sham组,n=10)、缺血再灌注组(I-R组,n=50)和后处理组(IP组,n=50),后两组根据再灌注时间又分为6、12、24、48、72h亚组(n=10)。I-R组:线栓大脑中动脉2h后,拔出线栓完成持续性再灌注,建立局灶脑缺血再灌注模型;IP组:大脑中动脉阻闭2h后,持续再灌注前行再灌注15s、缺血15s,反复3次;sham组:不施加缺血及再灌注处理。对各组大鼠进行神经行为学评分,行TTC染色测定脑梗死体积,免疫组化法检测脑组织TLR4和NF-κB蛋白的表达,原位杂交法检测TLR4和NF-κB mRNA的表达。结果 I-R组大鼠可见神经行为学的缺失及缺血侧大脑半球梗死。与I-R组相比,IP组大鼠脑梗死体积明显减小,神经行为学评分改善,差异有显著性(t=2.683～5.657,P<0.05)。TLR4、NF-κB蛋白及mRNA在sham组额顶叶有微弱表达,在I-R组和IP组的表达于再灌注6h时开始升高,24h达高峰(F=7.995～11.704,q=4.770～9.001,P<0.05);与I-R组各相应亚组比较,IP组TLR4、NF-κB蛋白及mRNA表达均明显降低,差异均有显著性(t=2.333～6.916,P<0.05)。结论 IP可下调TLR4和NF-κB的表达,减轻大鼠局灶性脑缺血再灌注损伤,改善神经功能。 Objective To investigate the effect of IP on the expression of TLR4 and NF-κB after focal cerebral ischemia-reperfusion in rats and to explore the role of TLR4-NF-κB signal The role of pathways in brain IP. Methods A total of 110 adult male Sprague-Dawley rats were randomly divided into three groups: sham operation group (sham group, n = 10), ischemia reperfusion group (n = 50) and postconditioning group (n = 50) The latter two groups were further divided into 6, 12, 24, 48 and 72h subgroups according to the reperfusion time (n = 10). IR group: After the middle cerebral artery was sutured for 2 hours, the rats were drawn out of the thrombus to complete the reperfusion and establish the model of focal cerebral ischemia / reperfusion. In the IP group, the middle cerebral artery blocked for 2h, then reperfused for 15s , Ischemia 15s, repeated 3 times; sham group: no ischemia and reperfusion treatment. The neurobehavioral scores of rats in each group were measured. The volume of cerebral infarction was determined by TTC staining. The expressions of TLR4 and NF-κB protein were detected by immunohistochemical method. The expressions of TLR4 and NF-κB mRNA were detected by in situ hybridization. Results I-R rats showed neurobehavioral deficits and ischemic hemisphere infarction. Compared with I-R group, the volume of cerebral infarction in IP group was significantly decreased and the neurobehavioral score was improved with significant difference (t = 2.683-5.657, P <0.05). The expressions of TLR4, NF-κB protein and mRNA in the frontal lobe of sham group were weakly expressed. The expression of TLR4 and NF-κB protein in the IR group and IP group began to increase at 6h and reached the peak at 24h (F = 7.995-11.704, q = 4.770-9.001 , P <0.05). Compared with the corresponding subgroups in IR group, the expressions of TLR4 and NF-κB protein and mRNA in IP group were significantly decreased (t = 2.333-6.916, P <0.05). Conclusion IP can down-regulate the expressions of TLR4 and NF-κB, reduce the focal cerebral ischemia-reperfusion injury and improve the neurological function.