复方地黄对帕金森病大鼠多巴胺能神经元及GDNF表达的影响

目的:研究复方地黄对6-羟基多巴胺(6-hydroxydopamine,6-OHDA)诱导的帕金森病(Parkinson’s disease,PD)大鼠多巴胺能神经元的保护作用及其可能机制。方法:40只SD雄性大鼠,分为正常组、假手术组、模型组、模型组+复方地黄组(即干预组)。观察PD大鼠药物诱发的旋转行为;免疫组化法观察黑质酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性神经元数目及胶质细胞源性神经营养因子(glial cell line-derivedneurotrophic factor,GDNF)表达水平的变化。结果:干预组与模型组间的旋转圈数有明显差异(P0.05);模型组黑质TH阳性神经元数目(52.9±2.2)明显少于正常组(160.3±2.4)、假手术组(161.6±3.4)及干预组(61.5±2.6)(P0.05);在大鼠黑质和纹状体部位,干预组GDNF阳性细胞数量比正常组、假手术组、模型组均明显增加(P0.05)。结论:复方地黄方能明显改善PD大鼠的旋转行为,拮抗6-羟基多巴胺诱导的PD大鼠黑质多巴胺能神经元的丢失,其保护作用可能与促进内源性GDNF分泌增加有关。

Effects of Compound Rehmannia on Dopaminergic Neurons And the Expression of GDNF in Parkinsonian Rats

Objective:To investigate the neuroprotective effects of compound rehmannia on dopaminergic neurons of Parkinsonian rat model induced by 6-hydroxydopamine(6-OHDA).Methods:The SD rats were divided into 4 groups:normal control group,sham operated group,6-OHDA group,compound rehmannia+6-OHDA group.The rotation behaviour in PD rats were observed.The number of tyrosine hydroxylase(TH) positive cells in the substantia nigra and the expression of glial cell line-derived neurotrophic factor(GDNF) were measured by immunohistochemistry.Results:The rats in compound rehmannia+6-OHDA group appeared obvious changes of rotation behaviour(P<0.05).The number of TH positive cells in the substantia nigra was significantly reduced in 6-OHDA group than that in compound rehmannia+6-OHDA group(P<0.05).The expression of GDNF in the substantia nigra and striatum was markedly increased in compound rehmannia+6-OHDA group than that in the other groups(P<0.05).Conclusion:Compound rehmannia could significantly improve the rotation behaviour of PD model rats,and partially block the loss of dopaminergic neurons of Parkinsonian rat model induced by 6-OHDA.The mechanism of neuroprotective effect may be related to the elevated secretion of endogenous GDNF.