PARP抑制剂3-AB对脂多糖诱导的帕金森病大鼠保护作用及可能机制  

The protective effect and possible mechanism of PARP inhibitior 3-AB on neuroinflammation in LPS-induced PD rats

作　　者：吴晓黎[1] 王萍[2] 刘云会[3] 薛一雪[2] 

机构地区：[1]中国医科大学附属盛京医院神经内科,辽宁沈阳110021 [2]中国医科大学基础医学院神经生物学教研室,辽宁沈阳110013 [3]中国医科大学附属盛京医院神经外科,辽宁沈阳110021

出　　处：《解剖科学进展》2015年第2期113-116,共4页Progress of Anatomical Sciences

基　　金：国家自然科学基金资助项目(81171131;81172197;81272564;81372484);沈阳市科学技术计划(F13-220-9-15;F13-316-1-16;F13-316-1-19)

摘　　要：目的研究PARP抑制剂3-氨基苯甲酰(3-aminobenzamide,3-AB)对脂多糖(lipopolysaccharide,LPS)诱导的帕金森病(Parkinson's disease,PD)大鼠的作用及机制。方法大鼠随机分三组:对照组,LPS组和LPS+3-AB组。免疫组化法检测黑质内酪氨酸羟化酶(tyrosine hydroxylase,TH)的表达;ELISA法检测IL-6和IL-10的蛋白含量;Western blot法检测ERK1/2,p-ERK1/2,p38MAPK,p-p38MAPK蛋白表达水平的变化。结果 LPS显著降低大鼠黑质内TH阳性细胞数,升高IL-6的表达水平,降低IL-10的表达水平,增加p-p38MAPK/p38MAPK和pERK1/2/ERK1/2的表达。PARP抑制剂3-AB显著增加TH阳性细胞数,降低IL-6的水平,增加IL-10的水平,降低pERK1/2/ERK1/2的表达,而使p-p38MAPK/p38MAPK的表达增加。结论 3-AB的脑保护作用可能与ERK1/2通路有关。Objective To investigate the role and possible mechanism of Poly（ADP-Ribose） polymerase（PARP） inhibitor 3-aminobenzoic acid（3-AB） in dopaminergic neurons in lipopolysaccharide（LPS）-induced Parkinson＇s disease（PD） rats. Methods The rats were divided into 3 groups randomly： sham-operated group, LPS group and LPS＋3-AB group. Immunohistochemical staining was used to determine the expression of tyrosine hydroxylase（TH）-immunoreactive neurons in substantia nigra（SN） of rats. ELISA was used to analyze IL-6 and IL-10 level in SN, Western blot was used to determine the expression of ERK1/2 and p38 MAPK phosphorylation.. Results LPS derceased the number of TH positive cells in SN, significantly upregulated the expression level of IL-6 and reduced the expression levels of IL-10. The effecs of LPS above-mentioned were significantly inhibited by pretreatment with PARP inhibitor 3-AB. 3-AB reduced the pERK1/2 expression, but increased the expression of p-p38 MAPK. Conclusion The protective effect of 3-AB on dopaminergic neurons might be related to modulation of ERK1/2 signal pathway.

关 键 词：帕金森氏病 炎症 PARP-1 脂多糖 ERK 

分 类 号：R742.5[医药卫生—神经病学与精神病学]