COX-2对帕金森病小鼠黑质内多巴胺能神经元的毒性作用

目的:观察环氧合酶-2(COX-2)对帕金森病(PD)模型小鼠黑质内多巴胺(DA)能神经元的损害作用.方法:采用Lau法制作PD小鼠模型,通过行为学观察,免疫组织化学和免疫蛋白印记法,观察PD小鼠模型的行为学表现,黑质致密部COX-2免疫反应阳性细胞,DA能神经元数量和腹侧中脑(包括VTA和SN)COX-2,酪氨酸羟化酶(TH)表达水平的变化,并观察给予COX-2抑制剂后对上述变化的影响.结果:与对照组小鼠相比,PD组小鼠出现PD典型的行为学表现,黑质致密部DA能神经元和腹侧中脑TH含量分别下降约63%和77%.同时,黑质致密部COX-2阳性细胞和腹侧中脑COX-2含量有大幅升高.经COX-2抑制剂处理的PD小鼠行为表现较轻,黑质致密部DA能神经元和腹侧中脑TH含量仅下降约37%和41%.与单纯PD小鼠比较,黑质致密部COX-2阳性细胞和腹侧中脑COX-2含量明显下降.结论:COX-2对PD模型小鼠黑质内DA能神经元有毒性作用.

Toxic effect of COX-2 on dopaminergic neurons of substantia nigra in mice with Parkinson's disease

AIM: To study the toxic effect of cyclooxygenase-2(COX-2) on dopaminergic(DA) neurons of the substantia nigra in mice of Parkinson's disease(PD).METHODS: The PD model was produced according to the Lau's method.The effects of COX-2 on the number of COX-2 immunoreactive cells and DA neurons in the substantia nigra pars compact(SNc),and the(expression) levels of COX-2 and tyrosine hydroxylase(TH) in ventral midbrain,including ventral tegmental area(VTA) and substantia nigra(SN),were studied with immunohistochemical(analysis) and Western blot.The changes of above mentioned(indexes,) after giving COX-2 inhibitor to those PD mice,were also studied.RESULTS: Compared with those control mice,the PD mice had the typical behaviors of PD,and the number of DA neurons in SNc and the level of TH in ventral midbrain decreased by about 63% and 77%.Meanwhile,the number of the COX-2-(positive) cells in SNc and the expression(level) of COX-2 in ventral midbrain increased markedly.The PD mice,administered additionally by COX-2 inhibitor,celecoxib,had slight behavioral symptoms,and the number of DA neurons in SNc and the expression level of TH in ventral midbrain declined by only about 37% and 41%;the number of the COX-2-positive cells in SNc and the expression level of COX-2 in ventral midbrain were obviously down-regulated,compared with those simple PD mice.CONCLUSION: COX-2 is toxic to DA neurons of the PD mice.