塞来昔布对脂多糖诱导的原代多巴胺能神经元变性的保护作用  

Celecoxib protects against dopaminergic neurons degeneration induced by lipopolysaccharides in rat primary midbrain cultures

作　　者：任士卿[1] 徐芳[1] 王彦勇[2] 王铭维[2] 

机构地区：[1]河北医科大学第三医院神经内科,河北石家庄050051 [2]河北省脑老化与认知神经科学实验室,河北石家庄050031

出　　处：《中风与神经疾病杂志》2008年第5期525-528,共4页Journal of Apoplexy and Nervous Diseases

摘　　要：目的研究COX-2选择性抑制剂塞来昔布对脂多糖诱导的中脑原代多巴胺能神经元变性的保护作用及其机制。方法将培养7d的孕14d SD大鼠胚胎中脑原代细胞随机分为4组:对照组、脂多糖(LPS)组(20ng/ml)、塞来昔布(20μmol/L)+脂多糖组、单纯塞来昔布组。培养72h后使用免疫荧光染色观察酪氨酸羟化酶(TH)、OX-42阳性细胞数目和形态变化,放免法测定上清液中前列腺素E2(PGE2)和肿瘤坏死因子-α(TNF-α)水平。结果塞来昔布+LPS组和LPS组比较:TH阳性细胞数目明显增多,分别为对照组的69%和48%(P<0.05);OX-42阳性细胞数目明显减少,分别为对照组的2和3.48倍(P<0.05)。形态上分析塞来昔布显著改善LPS对TH阳性细胞的损伤程度和抑制LPS诱导的小胶质细胞体积增大、形态不规则。同时抑制LPS诱导的PGE2和TNF-α含量的增加(P<0.05)。结论塞来昔布通过抑制小胶质细胞激活以及COX-2表达,减少细胞外PGE2、TNF-α水平发挥其神经保护作用。Objective To study the possible mechanism and neuroprotective effects of celecoxib against dopaminergic degeneration induced by lipopolysaccharides （LPS） in primary midbrain cell cultures. Methods Rat primary midbrain cultures were obtained from timed pregnant Sprague-Dawley rats on embryonic day 14.7d after seeding, the cultures were divided into 4 groups （n = 3 ） ：control group, LPS group（20ng/ml）, celecoxib group and celecoxib（20μmol/L） ＋ LPS group. 3d later,the positive cells and morphological changes of TH, OX-42 were observed by immunofluorescence. PGE2 and TNF- α in supernatants were measured by radioimmunoassay. Results The numbers of TH positive neurons in the group of pretreatment with celecoxib（20μmol/L） were more than those in LPS group, and was 69% and 48% of the control cultures respectively （P 〈 0.05）. The numbers of microglias were 200% and 348% of those of the c, ontrol respectively （P 〈 0.05 ）. Morphologically, celecoxib obviously attenuated the loss of TH neuronal process and inhibited morphological changes of microglia, and the irregular shape with enlarged cell body induced by LPS. The levels of PGE2 and TNF-α in supernatants were significantly inhibited by pretreatment with celecoxib. Conclusion Celecoxib protect dopaminergic neurons against LPS-induced neurodegeneration in primary midbrain cell cultures, and its protective effects may be associated with inhibiting microglial activation and suppression of COX-2 expression in activated microglia, then subsequently lessed the production of neurotoxic factors.

关 键 词：多巴胺能神经元 脂多糖 环氧化酶-2 塞来昔布 

分 类 号：R742.5[医药卫生—神经病学与精神病学]