【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。更多还原

【Abstract】 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.更多还原