苁蓉总苷对MPTP帕金森病模型小鼠脑黑质多巴胺能神经元保护作用的研究

作者	单位
李文伟	复旦大学附属中山医院、复旦大学中西医结合研究所神经病学研究室
杨茹	复旦大学上海医学院医学神经生物学国家重点实验室
蔡定芳	复旦大学附属中山医院、复旦大学中西医结合研究所神经病学研究室 (上海200032) 复旦大学上海医学院医学神经生物学国家重点实验室
王虎	复旦大学附属中山医院、复旦大学中西医结合研究所神经病学研究室 (上海200032) 复旦大学上海医学院医学神经生物学国家重点实验室

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中文摘要:

目的探讨苁蓉总苷对MPTP帕金森痛(PD)模型小鼠脑黑质多巴胺能(DA)神经元的保护作用。方法将小鼠随机分为正常组、模型组、苁蓉总苷高(400 mg/kg)、中(200mg/kg)、低(100 mg/kg)剂量组,各组在造模前3天灌服相应药物;采用MPTP(30 mg/kg)连续5天腹腔注射制作小鼠慢性PD模型,运用爬竿试验定量组织化学检测小鼠的神经行为,免疫组化法测定小鼠脑纹状体酪氨酸羟化酶(tyrosine hydroxy- lase,TH)阳性纤维表达以及黑质TH神经元数量的变化。结果在造模后7天和14天时,与模型组比较,苁蓉总苷高剂量组爬杆时间缩短(P<0.01),苁蓉总苷各剂量组纹状体TH阳性纤维的平均光密度值均明显增高(P<0.01);3个剂量组的苁蓉总苷均能对抗MPTP导致的TH阳性神经元数量减少,但只有高剂量组在两个时间点上与模型组的差异有统计学意义(P<0.05)。结论苁蓉总苷能够显著改善PD模型小鼠的神经行为、抑制脑黑质DA神经元的数量减少和纹状体TH表达的降低。

英文摘要:

Objective To investigate the protective effects of’ cistanehe total glycosides(CTG)on dopaminer- gie neuron in substantia nigra(SN)of model mice of Parkinson’s disease(PD).Methods Experimental mice were randomly divided into 5 groups,the normal control group,the model group,the high(400 mg/kg),moderate (200 mg/kg)and low(100 mg/kg)dose CTG groups.Mouse model of chronic PD was induced by peritoneal in- jection of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)30 mg/kg for 5 successive days.Climbing test was used to estimate the neurobehavior of mice on the 7th and 14th day(D7 and D14)after initiating MPTP injec- tion;meantime,quantitative immunohistochemistry was conducted to detect the number of dopaminergic neuron in SN and expression of tyrosine hydroxylase(TH)in striatum.Results The average time of climbing in the high dose CTG group on D7 and D14 was significantly shorter than that in the model group(P<0.01).The mean optic density(OD)of TH in striatum was higher in the three CTG groups than that in the model group on D7(P<0.01);but on D14,significance only showed in the high and moderate dose CT(,groups(P<0.01).Moreover, the MPTP induced decrease of TH positive neuron could be antagonized by CTO,but significant difference only showed between the high dose CTG group anti the model group at the two time points of observation(P<0.05). Conclusion CTG could improve the neurobehavior of PD model mice significantly,anti inhibit the decrease of ni- gral dopaminergic neurons and TH expression in striatum.

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