PARP抑制剂3-AB对脂多糖诱导的帕金森病大鼠血脑屏障及多巴胺能神经元的影响  

Effects of Poly(ADP-Ribose) polymerase inhibitor 3-AB on blood–brain barrier permeability and dopaminergic neurons 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110122 [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3期225-228,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：目的研究多聚ADP核糖聚合酶(poly(ADP-ribose)polymerase,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)大鼠的血脑屏障(blood–brain barrier,BBB)及多巴胺能神经元的影响。方法大鼠随机分三组:对照组,LPS组和LPS+3-AB组。用伊文思兰渗透性实验检测血脑屏障通透性;Western blot法检测MMP-9和紧密连接蛋白ZO-1的表达;免疫组化法检测MMP-9在黑质神经元的表达。结果与对照组比较,LPS组黑质内BBB的通透性和MMP-9的表达显著增加,紧密连接蛋白相关蛋白ZO-1的表达和酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性细胞数显著降低。上述作用受到PARP抑制剂3-AB的显著抑制。结论 3-AB通过保护LPS诱导的PD大鼠的BBB进一步保护多巴胺能神经元。Objective To investigate the role of PARP inhibitor 3-aminobenzoic acid（3-AB） in blood-brain barrier（BBB） permeability and 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. Evens blue（EB） assay was used to detect the permeability of BBB. Western blot was used to determine the expression of MMP-9 and tight junction associated protein ZO-1 in substantia nigra（SN） of rats. Immunohistochemical staining was used to determine the expression of tyrosine hydroxylase（TH）-immunoreactive neurons in SN. Results Compared with control group, the BBB permeability and the expression levels of MMP-9 of LPS group were increased significantly, and the expression levels of ZO-1 and the number of TH-positive cells in SN were decreased significantly. The above-mentioned effects of LPS were significantly inhibited by pretreatment with PARP inhibitor 3-AB. Conclusion PARP inhibitor 3-AB reduced BBB permeability and protected dopaminergic neurons.

关 键 词：帕金森氏病 多聚ADP核糖聚合酶 脂多糖 血脑屏障 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]