二苯乙烯苷通过抑制ROS减轻MPTP对帕金森病小鼠的神经毒性作用

TSG attenuated MPTP-induced neurotoxicology in Parkinson's disease mice by the inhibition of ROS

目的:探讨2,3,5,4’-四羟基二苯乙烯-2-o-β-D-葡萄糖苷(2,3,5,4’-tetrahydroxystibene-2-o-β-D-glucoside,TSG)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-pheyl-1,2,3,6-tetrahydrophridine,MPTP)诱导的帕金森病(Parkinson’s disease,PD)小鼠黑质多巴胺能神经元保护作用的机制。方法:实验分成三组,即健康C57BL小鼠随机分为对照组(腹腔注射生理盐水);模型组,连续7 d给C57BL小鼠腹腔注射MPTP(30 mg/kg)制备亚急性PD模型;治疗组,在给予MPTP后1 h腹腔注射TSG(60 mg/kg)。爬杆实验检测小鼠的行为学变化;活性氧(reactive oxygen species,ROS)检测试剂盒检测ROS水平;免疫荧光组织化学染色法测定黑质酪氨酸羟化酶(TH)和多巴胺转运体(DAT)的表达变化。结果:行为学:与对照组比较,模型组爬杆时间与转头时间明显延长(P<0.01),而治疗组较模型组时间缩短(P<0.05)。模型组ROS水平较对照组大幅度升高(P<0.01),治疗组较模型组明显下降(P<0.05)。免疫荧光染色:与对照组相比,模型组TH及DAT阳性神经元的数目明显减少(P<0.01),而治疗组TH及DAT阳性神经元数目减少的幅度明显有所下降(P<0.05)。结论:TSG对MPTP诱导的神经毒性具有保护作用,其机制可能与TSG抑制ROS有关。

Objective： To investigate the mechanism of 2,3,5,4＇-tetrahydroxystibene-2-o-13-D-glucoside （TSG） on do- paminergic neuron protection in substantia nigra pars compacta （SNpc） from MPTP （1-methyl-4-pheyl-1,2,3, 6-tetrahy- drophridine） induced injury in Parkinson＇s disease （PD） mice. Methods： C57BL mice were randomly divided into three groups. Control group were established by intraperitoneal injection of saline. Subacute PD model group were established by intraperitoneal injection of MPTP （30 mg/kg） for 7 consecutive days. The treatment group was established by intraper- itoneal injection of TSG （60 mg/kg）1 h after MPTP. The behavior changes of mice were observed by pole test. The reac- tive oxygen species （ROS） was mesured by ROS assay kit. The tyrosine hydroxylase （TH） and dopamine transpoter （DAT） positive cells were detected by immunofluorescence histochemical method. Results： Behavioral results showed that compared with control group, the time of mice climb to the bottom of the pole and turn around increased obviously （P 〈 0.01 ）, while the time of TSG pretreatment group decreased compared with MPTP group （ P 〈 0.05 ）. ROS level in MPTP group increased significantly compared with control group （P 〈 0.01 ）, TSG pretreatment group decreased obvious- ly compared with MPTP group （ P 〈 0.05 ）. Immunofluorescence histochemical staining results showed that the number of TH-and DAT-positive neurons decreased significantly compared with control group （ P 〈 0.01 ）, but the reduction rate in TSG pretreatment group was lower （P 〈 0.05 ）. Conclusion： TSG attenuates MPTP-induced neurotoxicity by the inhibi tion of ROS.