NF-κB在LPS诱导的帕金森病模型大鼠中的作用  

The Effects of NF-κB on Parkinson Disease Rat Model Induced by LPS

作　　者：王晓慧[1] 王枫[1] 刁欢[1] 骆文静[2] 曹瑞[1] 侯祥红[1] 蔡同建[2] 张建彬[2] 季爱玲[1] 

机构地区：[1]第四军医大学军事预防医学系营养与食品卫生学教研室,陕西西安710032 [2]第四军医大学军事预防医学系劳动与环境卫生学教研室,陕西西安710032

出　　处：《现代生物医学进展》2009年第21期4027-4029,4047,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金资助(No.30700667)

摘　　要：目的:研究NF-κB在脂多糖(LPS)诱导的帕金森病(PD)模型大鼠中的作用。方法:52只SD大鼠按体重随机分为3组,实验组(LPS组)、预防组(PDTC+LPS组)和对照组,每组14只:(1)实验组SD大鼠按体重50mg/kg经腹腔注射生理盐水后经脑立体定位单侧黑质注射LPS4μl/只(4μg/只)后7d制成帕金森病模型;(2)预防组SD大鼠按体重50mg/kg经腹腔注射PDTC1h后再经脑立体定位单侧黑质注射LPS4μl/只(4μg/只);(3)对照组SD大鼠按体重50mg/kg经腹腔注射生理盐水后经脑立体定位单侧黑质注射生理盐水4μl/只。7d后观察三组大鼠皮下注射阿扑吗啡后的行为学变化,采用免疫荧光法检测注射7d后黑质部NF-κBp65的表达,并用western blotting检测其蛋白表达。结果:7d后,实验组大鼠有明显的行为学变化,预防组和对照组则无异常行为学表现。免疫荧光结果显示,与注射对侧相比,实验组大鼠经脑立体定位注射内毒素LPS后,注射侧黑质部TH表达显著减少,而NF-κBp65阳性表达则显著增加,western blotting得到同样结果(P<0.05);预防组和对照组大鼠黑质部TH和NF-κBp65阳性表达无显著性变化,western blotting得到同样结果(P>0.05)。结论:NF-κB参与了LPS PD大鼠发病过程,黑质中NF-κBp65过度激活是LPS对大鼠造成损害作用的机制之一。预先使用PDTC对LPS PD鼠起到一定神经保护作用。Objective：To investigate the effects of NF-κB on Parkinson disease（PD） rat model induced by lipopolysaccharide（LPS） . Methods：Fifty-two SD rats were separated into three groups randomly by body weight,test group（LPS group） 、prevention group（PDTC＋LPS group） and control group,with fourteen rats in each group：（1） in test group,SD rats were administered by stereotaxic injection at a dose of 4 g/rat LPS.after 7 days in order to make PD model;（2） SD rats in the prevention group were pre-treated with PDTC at a dose of 50 mg/kg an hour before stereotaxic injected with LPS at 4 g/rat the same as in the test group;（3） in control group,rats were administered by stereotaxic injection at a dose of 4 l/rat physiological saline. After 7 days,hypodermic injection of apomorphine was given to three groups in order to observe their behavior change,then immumofluorescence staining was used to detect the expression level of NF-κBp65 protein in substantia nigra（SN） ,then western blotting. Result：After injected with LPS 7 days,rats in the test group have significant ethology change,in contrast to rats in the prevention group and the control group. Immumofluorescence manifested that rats in the test group,NF-κBp65 expression level has significantly increased in the injected SN,in contrast to PDTC＋LPS group and Control group（P〈0.05） . But in PDTC＋LPS group and Control group,there weren＇t significant variance.Western blotting received the same results. Conclusion：NF-κBp65 participated in the effect of LPS PD rat model,one of the mechanism of the damage of LPS to rat is too much activation of NF-κBp65 in SN. Pre-treated with PDTC has certain neuroprotective effect in LPS PD rats.

关 键 词：帕金森病(PD) 二硫代氨基甲酸吡咯烷(PDTC) 脂多糖(LPS) 核因子-κB (NF-κB) 

分 类 号：R742.5[医药卫生—神经病学与精神病学]