蛇床子素抑制核转录因子-κB的激活减轻β淀粉样蛋白25-35片段诱导的大鼠神经元结构损伤  

Osthole attenuates β-amyloid 25-35 induced neuronal injury through inhibition of nuclear factor-kappa B activation in rats

作　　者：刘远贵 李小慧[1] 邓媛媛[1] 龚其海[1] 

机构地区：[1]遵义医学院药理学教研室暨基础药理省部共建教育部重点实验室,贵州遵义563099

出　　处：《遵义医学院学报》2015年第5期470-473,共4页Journal of Zunyi Medical University

基　　金：教育部"长江学者和创新团队发展计划"创新团队项目(NO:IRT1197);贵州省科技厅优秀青年科技人才基金资助项目(NO:201326)

摘　　要：目的观察蛇床子素对β淀粉样蛋白25-35片段(Aβ25-35)诱导大鼠神经毒性的影响。并研究其可能机制。方法将30只雄性SD大鼠随机分为3组:假手术组、模型组和治疗组(n=10)。双侧海马注射Aβ25-35制模后,治疗组每日1次灌胃蛇床子素40 mg/kg,假手术组和模型组灌胃等体积溶媒,连续15 d后处死大鼠,每组随机取3只行HE染色观察神经元损伤情况,其余大鼠分别采用Western blot法检测IL-1β、TNF-α蛋白表达及p-NF-κB p65水平。结果模型组大鼠海马CA1区神经元较假手术组明显受损,且IL-1β、TNF-α蛋白表达及p-NF-κB p65水平增加(P<0.01);然而,蛇床子素减轻了Aβ25-35诱导的神经元损伤,降低了IL-1β(P<0.05)、TNF-α蛋白表达及p-NF-κB p65水平(P<0.01)。结论蛇床子素抑制NF-κB的激活,下调IL-1β、TNF-α蛋白表达,可能是其轻减Aβ25-35所致大鼠神经元损伤的机制之一。Objective This study was designed to investigate the effect of osthole on neurotoxicity induced by β - amyloid 25 - 35 in rats, and explore its potential mechanisms. Methods Male Sprague - Dawley rats were randomly divided into three groups： sham group, model group and osthole -treated group. The rat model of neurotoxicity was induced by injecting Aβ26-35 into the bilateral hippocampus. Then treated groups were administrated with osthole （40 mg/kg per day, po） for 15 d, while rats in sham and model groups were administrated with volume-matched vehicle. Hippocampal neuronal injury was observed by Haematoxylin- Eosin staining and the protein expressions of IL - 1β, TNF -α, and the level of p - NF - κB p65, were detected by Western blot . Results Administration of Aβ25-35 to bilateral hippocampus significantly caused neuronal injury in CA1 region, and increased the protein expression of IL - 1β, TNF - α, and the level of p - NF -κB p65 compared with those in sham operation group （P 〈 0.01 ）. However, treatment with osthole significantly attenuated neuronal injury and reduced the protein expression of IL - 1β （ P 〈 0.05 ） , TNF - α, and the level of p - NF - κB p65 compared with model group （P 〈 0.01 ）. Conclusion Osthole attenuates neuronal injury induced by Aβ25-35 in rats through suppressing NF - κB activation, reducing the protein expression of IL - 1β, and TNF -α.

关 键 词：蛇床子素 Β淀粉样蛋白25-35 核转录因子-ΚB 炎症 大鼠 

分 类 号：R965[医药卫生—药理学]