NFκB在大鼠局灶性脑缺血预处理抗细胞凋亡中作用的研究

Effect of nuclear factor-κB on the anti-apoptosis induced by focal ischemia preconditioning in Wistar rats

目的研究NFκB在大鼠局灶性脑缺血预处理抗细胞凋亡中作用。方法采用开颅方法阻断大鼠大脑中动脉(MCAO),通过脑梗塞体积分析及病理形态学变化,观察脑缺血预处理的保护作用。采用TUNEL的方法检测神经细胞的凋亡程度。免疫组化染色和细胞化学方法检测脑组织核转录因子NFκBp65蛋白的表达和超氧歧化酶(SOD)活性、丙二醛(MDA)水平的变化。结果预处理未引起脑组织神经元的病理性损伤,相对于未经预处理的缺血组,经预处理的脑缺血组脑组织梗塞体积显著减小,半影区凋亡细胞数明显减少,且细胞核NFκBp65蛋白表达显著增加,脑组织SOD的活性亦明显增大,MDA值明显减小(均P<0.01)。结论缺血预处理能够减轻再次的缺血性损伤所诱导的神经细胞凋亡。NF-κB可能是缺血预处理保护中抗凋亡信号调节的关键步骤之一。

AIM: To explore the effect of nuclear factor-κB (NF-κB) on the anti-apoptosis induced by brain ischemia preconditioning (IP). METHODS: Temporary middle cerebral artery occlusion for 20 min followed three days reperfusion before 6 hours middle cerebral artery occlusion (MCAO) trancranially was used as preconditioning in Wistar rats. The protective role was evaluated by analyzing the infarct volume. The status of neuronal apoptosis was observed by TUNEL. The expression of NFκB p65 protein, the assay of SOD activity and MDA concentration were analyzed by using the methods of immunohistochemistry and cytochemistry. RESULTS: Compared to the control group, 20 min ischemic preconditioning, which did not produce neuronal damage obviously, reduced the infarct volume significantly after MCAO 6 h and obviously decreased the number of neural cell apoptosis in penumbra (P<0.01). The expression of NFκB p65 protein and the activity of SOD were extensively increased. The concentration of MDA was decreased in IP cortex and white matter in ischemic group with preconditioning. CONCLUSION: These results indicate that IP is capable of activating NF-κB that in turn increases the expression of genes and participates in IP-induced protective responses to apoptosis.