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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
【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。
【Abstract】 ObjectivesTo 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 (MPTP) induced C57BL6 mice. Methods Thirty male C57BL6 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. ResultsCompared 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 Celecoxib 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.
- 【文献出处】 中国现代医学杂志 ,China Journal of Modern Medicine , 编辑部邮箱 ,2009年14期
- 【分类号】R742.5
- 【被引频次】3
- 【下载频次】176