缺血后处理下调大鼠脑缺血再灌注时TLR4和NF-кB表达

Ischemic postconditioning down-rugulate expression of TLR4 and NF-кB during cerebral ischemla/reperfusion in Rats

目的探讨缺血后处理(IP)对大鼠局灶性脑缺血再灌注时Toll样受体4(TLR4)和核因子-кB(NF-кB)表达的影响。方法将110只成年健康雄性SD大鼠随机分为假手术(sham)组(n=10)、缺血再灌注(I/R)组和后处理(IP)组,后两组根据再灌注的不同时间各分为6h、12h、24h、48h、72h 5个亚组(n=10)。建立局灶缺血再灌注和缺血后处理模型。观察大鼠的神经行为学评分、脑梗死体积、额顶叶皮层TLR4、NF-кB蛋白及mRNA表达情况。结果与I/R组相比,IP组大鼠神经行为学评分显著改善,脑梗死体积明显减少(P<0.05)。TLR4、NF-кB蛋白在I/R组和IP组的表达于再灌注6h时开始升高,24h达高峰。与I/R各相应亚组比较,IP各亚组TLR4、NF-кB蛋白表达均明显降低(P<0.05)。TLR4、NF-кB mRNA在I/R组和IP组的表达时间曲线与蛋白相一致。结论IP可通过抑制TLR4和NF-кB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 effects of ischemic postconditioning on the expression of Toll-like receptor 4 （TLR4） and Nuclear factor-кB （NF-кB） during focal cerebral ischemic reperfusion in rats. Methods One hundred and ten adult healthy male Sprague-Dawley rats were randomized into sham group （n = 10）, ischemic reperfusion group （I/R group） andischemic postconditioning group （ IP group）. The latter two groups were equally divided into five subgroups according to different time points of the ischemic reperfusion （6,12,24,48 and 72h） （n = 10 ,respectively）. Both focal cere- bral ischemic reperfusion and ischemic postconditioning was established. The neurobehavioral function deficit scores,infarct volume and the expression of TLR4 protein,NF-KB protein,TLR4 mRNA and NF-KB mRNA in the frontoparietal cortex at the corresponding time points were observed. Results Compared with the I/R group, the IP group showed improved neurobehavioral function deficit scores and reduced cerebral infarct volume （P 〈 O. 05 ）. TLR4 protein and NF-KB protein ex- pression significantly increased in I/R group and IP group at 6h following reperfusion, peaked at 24h,however, the positive products in IP group were significantly lower than those in L/R group at each time point after reperfusion （ P 〈 0.05 ）. TLR4 mRNA and NF-KB mRNA expression were consistent with TLR4 protein and NF-кB protein. Conclusion IP could reduce infarct volume and improve neurobehavioral function through inhibiting the expressions of TLR4 and NF-кB.