选择性环氧化酶-2抑制剂对MPTP致帕金森病模型小鼠多巴胺能神经元保护作用的研究  

Neuroprotective effects of Celecoxib on the dopaminergic neurons in the substantia nigra in MPTP-induced C57BL6 mice

作　　者：成志[1] 

机构地区：[1]南华大学第一附属医院神经内科,湖南衡阳421001

出　　处：《中国现代医学杂志》2009年第14期2160-2162,2167,共4页China Journal of Modern Medicine

摘　　要：目的探讨选择性环氧化酶-2(COX-2)抑制剂塞来昔布对1-甲基4-苯基-1,2,3,6-四氢吡啶(1-methy-4-phenyl-1,2,3,6-tetra-hydropyridine,MPTP)致帕金森病小鼠黑质多巴胺(dopamine,DA)能神经元变性的保护作用及其可能机制。方法30只健康雄性C57BL6小鼠随机分成3组:PBS对照组、生理盐水治疗组(生理盐水+MPTP)和塞来昔布治疗组(塞来昔布+MPTP),每组各10只。采用免疫组织化学法观察大鼠黑质酪氨酸羟化酶(TH)阳性细胞的减少,免疫印迹法检测黑质COX-2蛋白表达。结果与PBS对照组比较,生理盐水治疗组TH阳性细胞明显减少(P<0.05),黑质COX-2蛋白表达明显增加,塞来昔布治疗组TH阳性细胞数较生理盐水治疗组明显增多(P<0.05),黑质COX-2蛋白表达含量明显减少。结论COX-2的表达与PD模型小鼠黑质内DA能神经元的丢失有关,塞来昔布可能对PD模型小鼠黑质内DA能神经元有保护作用。[Objectives] To investigate whether Celecoxib can prevent the degeneration of dopaminergic neurons in the substantia nigra （SN） in 1-methy-4-phenyl-1, 2, 3, 6-tetra -hydropyridine （MFIIa） induced C57BL6 mice. [Methods] Thirty male C57B1_6 mice were randomly divided into three groups： PBS group, physiologic saline ＋ MPTP group and Celecoxib ＋ MPTP group. The number of tyrosine hydroxylase （TH）- positive neurons and the morphological changes of COX-2 positive microglias in the substantia nigra （SN） were observed by immunohistochemistry. COX-2 protein expression was examined by immuno blotting. [Results] Compared with PBS control group, TH-positive neurons in the saline plus MPTP group were obviously reduced （P 〈0.05）, COX-2 protein expression in the saline group was upregulated. Compared with the saline group, TH-positive neurons survived in Celecoxib group were upregulated, （P 〈0.05） and Celeeoxib significantly decreased the levels of COX-2 protein expression. [ Conclusion] The loss of DA neurons in the substantia nigra has correlation with the expression of COX-2. Celecoxib could protect the DA neurons in the substantia nigra.

关 键 词：帕金森病 多巴胺 环加氧酶抑制药 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]