摘要
目的研究中药单体成分红景天甙(salidroside)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱发的帕金森病(Parkinson disease,PD)小鼠模型的脑保护作用及其可能机制。方法80只C57BL雄性小鼠,分为正常对照组、MPTP模型组、MPTP+红景天甙组(即干预组,分别用3 mg/kg、50 mg／kg和150 mg／kg)及红景天甙对照组(分别用3 mg／kg、50 mg/kg和150 mg／kg),每组10只。应用免疫组化法观察黑质酪氨酸羟化酶(TH)阳性神经元数目变化,蛋白印迹法(Western blot)检测TH、胶质细胞源性神经营养因子(GDNF)、胶质纤维酸性蛋白(GFAP)在纹状体中表达水平的变化。结果在小鼠黑质部位,MPTP组TH阳性神经元数目明显少于正常对照组及干预组(P<0．05)。Western blot结果显示,不同剂量干预组小鼠纹状体中的TH蛋白表达(相对灰度值)(0．8326±0．0930．0．9007±0．0104和1．1114±0．2013)较MPTP组的TH蛋白表达(0．5738±0．01真4)明显增加(P< 0．05);干预组的GDNF蛋白表达(1．3503±0．0573)较MPFP组的蛋白表达(0．1485±0．0118)显著增加(P<0．05);干预组的GFAP蛋白表达(2．4788±0．2093)与MPTP组(1．8431±0．1559)之间差异无统计学意义(P>0．05),但是干预组较正常对照组(1．3695±0.1174)明显增加(P<0．05)。结论红景天甙可以拮抗MPTP诱导的PD模型小鼠黑质多巴胺能神经元的丢失,其神经保护作用可能与促进内源性GDNF分泌增加有关。
Objective To investigate the neuroprotective effects of salidroside on dopaminergic neurons of Parkinsonian mouse model induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine （MPTP）. Methods The C57BL mice were divided into 4 groups： MPTP group, MPTP ＋ salidroside group, saline control group and salidroside control group. The number of tyrosine hydroxylase （TH） positive cells in the substantia nigra was measured by immunohistochemistry. The expression of TH, glial cell line- derived neurotrophic factor （GDNF） and glial fibrillary acidic protein （GFAP） was detected by Western blot. Results The number of TH positive cells in substantia nigra was significantly reduced in MPTP group than that in MPTP 4- salidroside and saline control groups （ P 〈 0. 05 ）. The expression of TH proteins was obviously increased in MPTP ＋ salidroside group at different doses of salidroside （ relative grey scale being 0.8326±0.0930, 0.9007 ±0.0104 and 1.1114 ±0.2013 respectively） than that in MPTP group （0. 5738 ±0. 0114, P 〈 0. 05 ）. The expression of GDNF proteins was markedly increased in MPTP ＋ salidrosidegroup （1.3503 ±0.0573） than that in MPTP group （0.1485 ±0.0118, P 〈0.05）. Nostatistically significant difference of GFAP proteins was noted between the MPTP group and MPTP ＋ salidroside group （ P 〉 0. 05 ）, but the expression of GFAP proteins was remarkably elevated in MPTP ＋ salidroside group than that in saline control group （ 1. 3695 ±0. 1174, P 〈 0. 05 ）. Conclusions Salidroside could partially block the loss of dopaminergic neurons in the parkinsonian mouse model induced by MPTP. The mechanism of neuroproteetive effect may be related to the elevated secretion of endogenous GDNF.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2006年第8期540-543,共4页
Chinese Journal of Neurology
基金
国家重点基础研究发展计划资助项目(2006cb500706)
上海市重大基础研究资助项目(04DZ14005)
上海市博士后基金资助项目(05R214125)
中国博士后基金资助项目(2005038433)
作者简介
通信作者：陈生弟,Email：chen_sd@medmail.com.cn
