摘要目的 探讨急性坏死性胰腺炎(ANP)大鼠合并脑损伤时脑组织海马神经元凋亡及其与NF-κB p65之间的关系.方法 64只SD大鼠按数字表法随机分为生理盐水(NS)组和ANP组.胰胆管逆行注入4%牛磺胆酸钠制备ANP模型.尼氏染色法检测脑组织海马神经元的损伤,TUNEL法检测神经元凋亡,RT-PCR法及免疫组化法检测海马组织NF-κB p65 mRNA和蛋白的表达.结果 ANP组大鼠海马神经元缺失,胞核固缩,核仁欠清晰,尼氏小体减少或消失,损伤随时间延长逐渐加重.ANP组大鼠制模后3、6、12 h的神经元凋亡指数分别为10.63±0.24、21.02±0.25、17.12±0.36,显著高于NS组同时点的0.33±0.19、0.71±0.67、0.45±0.33(P值均＜0.01);NF-κB p65 mRNA表达量分别为0.63±0.05、1.05±0.06、0.92±0.05,显著高于NS组同时点的0.11±0.01、0.12±0.01、0.08±0.01(P值均＜0.05).NF-κB p65蛋白的变化与其mRNA的变化一致.结论 ANP大鼠脑损伤的早、中期与神经元凋亡关系密切,其机制可能与NF-κB p65的激活有关.

abstractsObjective To investigate the relationship between expression of nuclear factor kappa B p65 ( NF-κB p65) and hippocampal neuronal apoptosis in acute necrotizing pancreatitis (ANP) rats with brain injury. Methods Sixty-four SD rats were randomized into normal saline group (NS) and ANP group. The ANP rat model was induced by retrograde injection of 4% sodium taurocholate into the pancreaticobiliary duct of SD rats. Nissle stain was used to detect the brain injury. Neuronal apoptosis was determined by TUNEL.NF-κB p65 expression was detected by immunohistochemistry and RT-PCR. Results Hippocampal neuron was absent, karyopyknosis, unclear nucleolus and decreased Nissl bodies were found, the injuries was aggravated with time. The apoptosis index at the 3, 6 and 12 h in ANP group was 10.63 ±0.24, 21.02±0.25, 17.12±0.36, respectively, while they were 0.33±0.19,0.71±0.67, 0.45 ± 0. 33 in NS group, and the difference was statistically significant ( P ＜ 0. 01 ). The expressions of NF-κB p65 mRNA were 0. 63 ± 0.05,1.05 ±0.06,0.92 ±0.05, which were significantly higher than those in the NS group (0.11 ±0.01,0.12±0.01,0.08±0.01,P＜0.05).The chatge of expression of NF±κB p65 protein was consistent with that of NF-κB p65 mRNA. Conclusions The brain injury of ANP rats was highly correlated with neuronal apoptosis at the early and middle phase of ANP, and its mechanism may be related with NF-κB p65 activation.