摘要
目的观察塞来昔布(CB)对脂多糖(LPS)所致大鼠黑质多巴胺能(DA)神经元损伤的保护作用。方法黑质内注射LPS制作帕金森病(PD)大鼠模型。应用CB对实验动物进行处理。采用行为学、酪氨酸羟化酶(TH)、环氧化酶-2(COX-2)等免疫组化及免疫印迹技术观察CB的神经保护作用。结果对照组大鼠无行为变化,PD组大鼠平均旋转圈数为196.90±9.52,CB组为109.30±9.38,差异非常显著(P<0.01)。TH免疫组化表明,对照组TH阳性神经元数量较多,胞体较大,突起明显;PD组神经元数量明显减少或消失(P<0.01),神经元胞体萎缩,突起不清晰;CB组TH阳性神经元数与PD组相比明显增加(P<0.01),神经元形态变化亦不明显。COX-2免疫组化表明,对照组黑质偶见COX-2阳性细胞,PD组见大量COX-2阳性细胞;CB组COX-2阳性细胞数与PD组相比明显减少(P<0.01)。小胶质细胞特异性抗体(OX-42)免疫组化表明,对照组小胶质细胞多呈静止的"分枝样"状态;PD组多为激活状态,呈典型的"阿米巴样";CB组激活状态的小胶质细胞与PD组相比明显减少,形态为高度分枝状态。Western blotting分析结果相同。结论CB可防护LPS所致黑质DA能神经元损伤,具有神经保护作用。
Objective To observe the neuroprotective effect of celecoxib against degeneration of dopaminergic neurons caused by lipopolysaccharide in vivo. Methods The rat model of Parkinson disease （PD）was established by intranigral injection of lipopolysaccharide. Sprague-Dawley rats were randomly divided into control group,PD group,and celecoxib group. Behavioural changes were recorded,and the expressions of tyrosine hydroxylase （TH）and cyclooxygenase-2 （COX-2）were determined by immunohistochmistry and Western blot. Results No behavioral change was found in control group. There was significant difference in the number of circling behavior between PD and celecoxib groups （196.90±9.52 vs 109.30±9.38,P 0.01）. The number of TH-positive cells and the expression of TH protein in rat substantia nigra were significantly higher in celecoxib group than in PD group（P 0.01）. Compared with PD group,the number of COX-2positive cells and the expression of COX-2 protein were significant lower in celecoxib group（P 0.01）. Conclusion Celecoxib has neuroprotective effect on the degeneration of dopaminergic neurons caused by lipopolysaccharide in vivo.
出处
《中国医科大学学报》
CAS
CSCD
北大核心
2010年第3期191-193,204,共4页
Journal of China Medical University
基金
辽宁省自然科学基金资助项目(20052072)
关键词
塞来昔布
多巴胺能神经元
脂多糖
神经炎症
celecoxib
dopaminergic neuron
lipopolysaccharide
neuroinflammation
