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 there were significantly more ex-pression of TH positive cells and GDNF positive cells at subgroup of 8 day treatment compared with those at subgroup of 4day treatment within Eldepryl group with（all P〈0.05）. Conclusion These data suggest that Eldepryl can protect the dam-age of dopaminergic neurons in substantia nigra and striatum of PD rats. And its therapeutic mechanism may be associatedwith increased expression of GDNF.
出处
《天津医药》
CAS
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)
