二苯乙烯苷对帕金森病模型大鼠行为学及多巴胺能神经元的影响  

Neuroprotective effect of tetrahydroxystilbene glucoside on the rat model of Parkinson's disease

作　　者：贾新[1] 陈建宗[1] 杨志福[2] 陈宏[1] 张金平[1] 张娟[1] 蒋伟峰[1] 

机构地区：[1]第四军医大学西京医院中医药研究所,西安710032 [2]第四军医大学西京医院药剂科,西安710032

出　　处：《中国新药杂志》2008年第9期748-752,共5页Chinese Journal of New Drugs

摘　　要：目的:观察何首乌主要有效成分二苯乙烯苷(TSG)对帕金森病(PD)模型大鼠行为学及脑内黑质多巴胺能神经元的影响。方法:采用6-羟基多巴胺(6-OHDA)单侧脑内黑质致密部(SNC)和中脑腹侧被盖区(VTA)两点注射法制备PD大鼠模型后,灌胃给予TSG低、中、高剂量(50,100,200 mg·kg^(-1)),qd,连续5周。实验同时设正常对照组和美多芭阳性对照组(125 mg·kg^(-1)),每组10只。用旋转行为检测及Rotarod试验观察各组大鼠的行为学变化,用免疫组化法观察大鼠脑黑质酪氨酸羟化酶(TH)阳性神经元的表达,用高效液相色谱-电化学法(HPLC-ECD)测定大鼠脑黑质多巴胺(DA)及3,4-二羟基苯乙酸(DOPAC)含量。结果:行为学检测结果表明,模型组大鼠旋转次数及运动协调性均低干正常对照组(P<0.01),而TSG与美多芭给药可改善大鼠旋转行为及运动协调性。TH免疫组化检测结果显示,TSG处理组脑黑质部位损毁较轻,有较多残存的TH阳性细胞;而模型组黑质大部损毁,几乎无残存的TH阳性细胞;从HPLC-ECD测定结果可以看出,与正常对照组比较,模型组DA及DOPAC含量下降显著(P<0.05),与模型组相比,TSG处理组脑内DA及DOPAC含量明显增加(P<0.05)。结论:TSG可改善PD大鼠的行为学改变,增加黑质-纹状体多巴胺及其代谢物含量并提高黑质多巴胺能神经元的残存率,提示TSG对PD可能具有一定的神经保护作用。Objective ： To explore the neuroprotective effects of 2,3,5,4＇-tetrahydroxystilbene-2-O-β-D- glucoside （TSG） on Parkinson＇s disease （PD） rat model. Methods： The PD rat model was established by microinjection of 6-hydroxydopamine solution into fight ventral tegmental area （VTA） and substantia nigra pars compacta （SNC） of the mesencephalon. TSG （ 50,100 or 200 mg·kg^-1） was ig administered to the PD model rats once a day for 5 weeks. Healthy rats and madopar （ 125 mg·kg^-1） -treated rats were also used as normal and positive control. respectively. Each group contained 10 rats. Five weeks later, the behavior changes of rats were observed by the apomorphine-induced turning test and Rotarod test; the tyrosine hydroxylase （TH） positive cells were detected by immunohistochemical method; and dopamine and its metabolic products in nigrostriatal system of each group were determined by HPLC-ECD. Results ： PD model rats showed the behavior deficit. The number of left-turning in 30 min induced by apomorphine was significantly more and the rotation latency period was significantly less in the PD model group than those in the normal control group （P 〈0.01 ） ; however, TSG and madopar significantly reversed the behavior deficit （P 〈 0.05 ）. The number of TH-positive neurons and the content of DA and DOPAC were significantly reduced in the model group, and TSG inhibited the loss of TH-positive neurons and increased the content of DA and DOPAC in substantia nigra （P 〈 0.05 ）. Conclusion： TSG could efficiently improve the behavior changes in PD model rats, and protect the parkinsonian model against 6-OHDA-induced neuronal death by reducing DA neuron loss and increasing DA content.

关 键 词：二苯乙烯苷 帕金森病 行为学 酪氨酸羟化酶 多巴胺 

分 类 号：R285.5[医药卫生—中药学] R286.1[医药卫生—中医学]