司来吉兰对帕金森病模型大鼠黑质纹状体TH及GDNF表达的影响  

Effects of Eldepryl on TH and GDNF expressions in substantia nigra and striatum in Parkinson's disease model in rat

作　　者：吕超男[1] 毛文静[1] 马原源[1] 刘斌[1] 张晋霞[1] 孙静[1] 成晓华 李世英[1] 

机构地区：[1]河北联合大学附属医院神经内一科,063000

出　　处：《天津医药》2015年第2期154-157,I0002,共5页Tianjin Medical Journal

基　　金：河北省医学科学研究重点课题(20130064)

摘　　要：目的观察司来吉兰对帕金森病(PD)模型大鼠黑质纹状体内酪氨酸羟化酶(TH)及胶质细胞源性神经营养因子(GDNF)表达的影响,探讨司来吉兰对多巴胺能神经元的保护作用及机制。方法 72只健康雄性SD大鼠随机分为对照组、模型组和司来吉兰组,每组均设4 d和8 d 2个亚组,各12只。模型组和司来吉兰组采用颈背部皮下注射鱼藤酮制备PD模型,对照组皮下注射等体积葵花油。之后司来吉兰组每日灌胃咪多吡0.5 mg/kg,模型组和对照组每日灌胃等体积生理盐水,4 d和8 d组分别连续灌胃4 d和8 d。采用免疫组化法和Western blotting法检测黑质纹状体TH和GDNF表达水平。结果免疫组化法和Western blotting法检测结果均显示,对照组大鼠黑质纹状体可见多量TH阳性细胞表达和少量GDNF阳性细胞表达,8 d和4 d组差异均无统计学意义。模型组TH和GDNF阳性细胞表达均明显低于对照组(均P<0.05),8 d和4 d组差异均无统计学意义。司来吉兰组TH阳性细胞表达低于对照组而高于模型组,GDNF阳性细胞表达高于对照组和模型组(均P<0.05),且8 d组均高于4 d组(均P<0.05)。结论司来吉兰可减轻PD模型大鼠黑质纹状体多巴胺能神经元的损伤,其作用机制可能与增加GDNF表达有关。Objective To observe the effects of Eldepryl on expressions of tyrosine hydroxylase（TH） and glial cellline-derived neurotrophic factor（GDNF） in substantia nigra and striatum in Parkinson＇s disease（PD） and to explore theprotective mechanism of Eldepryl on dopaminergic neuron. Methods Healthy male Sprague-Dawley（SD） rats（n=72） wererandomly divided into control group, model group and Eldepryl group（n=24 in each group）. Each group was divided random-ly into 2 subgroups as 4 day treatment group and 8 day treatment group（n=12 in each subgrop）. Pakinson＇s disease modelwas established by injecting rotenone subcutaneously back the neck, rats in the control group were injected with an equal volume of sunflower oil subcutaneously at the same location. Rats in the Eldepryl group were then given Eldepryl 0.5 mg·kg-1in-tragastrically every day for 4 or 8 consecutive days and rats in model group and control group were given an equal volume ofsaline instead. The expression of TH and GDNF in substantia nigra and striatum were detected by immunohistochemistry andWestern blotting. Results Immunohistochemistry and Western blotting showed that strong expression of TH positive cellswith little expression of GDNF positive cells were seen in substantia nigra and striatum in rats of control group, and there wasno significant difference between subgroup of 8 day treatment and 4 day treatment within control group. The expression ofTH cells and GDNF were both significantly reduced in model group compared with those in control group（both P〈0.05）,and there was no significant difference between subgroup of 8 day treatment and 4 day treatment within each group. The ex-pression of TH positive cells were significantly reduced in Eldepryl group compared with those in control group, and were sig-nificantly increased compared with those in model group. The expression of GDNF positive cells were significantly increased in Eldepryl group compared with those in control group and model group（all P〈0.05）. And

关 键 词：帕金森病 酪氨酸单氧化酶 胶质细胞源性神经营养因子 多巴胺 单胺氧化酶抑制剂 酪氨酸羟化酶 司来吉兰 

分 类 号：R742.5[医药卫生—神经病学与精神病学]