目的：探讨地塞米松预处理对新生大鼠缺氧缺血后脑内NF κB活性及神经细胞凋亡的影响。方法：4 2只新生大鼠随机分为 5组 ,即正常对照组 (n =8) ,假手术组 (n =8) ,缺氧缺血组 (HIBD ,n =8) ,地塞米松治疗组 (DEX ,n =9)及地塞米松预处理组 (P DEX ,n =9)。于缺氧缺血 (HI)后 72h取脑 ,以Western印迹法检测脑组织中NF κB抑制蛋白IκBα表达 ,TUNEL法检测细胞凋亡 ,免疫组织化学法检测NF κB亚基p6 5核移位情况 ,免疫荧光双标法检测P6 5核移位与细胞凋亡共表达。结果：与正常对照组和假手术组比较 ,HIBD组及DEX组 p6 5阳性细胞及TUNEL阳性细胞数明显增加 (P <0 .0 1) ,IκBα蛋白表达明显减少 (P <0 .0 1)。P DEX组也可见p6 5阳性细胞及TUNEL阳性细胞表达 ,但较HIBD组及DEX组明显减少 (P <0 .0 1) ,而IκBα蛋白表达明显增多 (P<0 .0 1)。直线回归分析显示 ,在HIBD组中NF κB的活化与缺氧缺血后神经细胞凋亡密切相关 (r =0 .775 ,P <0 .0 1)。结论：NF κB的活化与缺氧缺血后神经细胞凋亡密切相关。DEX预处理对缺氧缺血性脑损伤的保护作用可能与抑制NF κB的活化 ,减少细胞凋亡有关。

OBJECTIVE: Previous studies suggest that dexamethasome (DEX) pretreatment can reduce hypoxic-ischemic brain damage (HIBD), but the mechanism for this effect has not been identified. This study examined the effects of DXM pretreatment on NF-κB activation and neuronal apoptosis in the brain of neonatal rats with HIBD, in order to identify a possible mechanism for the protective effect of DEX pretreatment in HIBD. METHODS: Forty-two 6-day-old Sprague-Dawley (SD) rats were randomly assigned to 5 groups: Normal controls (n=8), Sham-operated (n=8), HIBD (n=8), DEX pretreated (P-DEX, n=9) and DEX treated (DEX, n=9).HIBD was induced by hypoxia exposure combined with ligation of the left common carotid artery. DEX (0.1 mg/kg) was administered to rats in the P-DEX group 24 hrs before HI and to rats in the DEX group immediately after HI. After 72 hrs of HI, the rats were sacrificed and then the brain tissues were removed. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). The expression of p65 protein in tissue sections was detected by immunohistochemistry. The expression of IκBα protein was measured by Western blotting. Co-localization of p65 protein expression and apoptosis was determined with double-label immunofluorescence. RESULTS: The number of p65 positive cells and apoptotic cells was greater and the expression of the IκBα protein was less in the HIBD and DEX groups (P< 0.01) when compared with the Normal control and Sham-operated groups (P< 0.01). There were fewer p65 positive cells and apoptotic cells, and the level of IκBα protein expression was greater in the P-DEX group (P< 0.01) compared with the HIBD group. There were no significant differences between the DEX and HIBD groups. In the HIBD group, the level of NF-κB activation and the extent of neuronal apoptosis were significantly correlated (r= 0.775, P< 0.01). CONCLUSIONS: The activation of NF-κB may play an important role in the development of neuronal apoptosis in neonatal rats with HIBD. The protective effects of DEX pretreatment may work through the inhibition of NF-κB activation which may then inhibit neuronal apoptosis.