雌激素对PD模型大鼠黑质纹状体通路的保护作用及其机制探讨

The Protective Effect of Estrogen on Nigrostriatal System in The Rat Model of Parkinson's Disease and The Mechanism

目的研究雌激素(Estrogen)对6-羟基多巴(6-OHDA)制备的去卵巢(OVX)帕金森病(PD)模型大鼠黑质纹状体通路的保护作用及其可能机制。方法应用6-OHDA两点注射单侧损毁内侧前脑束(MFB)制备OVXPD模型大鼠,侧脑室给予17-β雌二醇(17-βestradiol,1μg/5μl),观察大鼠旋转行为、黑质酪氨酸羟化酶(TH)基因表达、黑质铁染色阳性细胞数量和纹状体内多巴胺(DA)及其代谢产物含量的变化。结果雌激素用药组可明显减少阿朴吗啡诱导的PD模型大鼠单侧旋转行为(P<0.01)。在损毁侧黑质,雌激素用药组TH基因的表达较PD模型组明显增加(P<0.01);纹状体DA及其代谢产物亦较PD模型组显著升高(P<0.01)。黑质铁染色阳性细胞数量较PD模型组明显减少(P<0.01)。结论雌激素对PD模型大鼠黑质DA能神经元有明显的保护作用,其作用机制可能与降低铁负载有关。

Ahn To investigate the protective effect of estrogen on the nigrostriatal system in the rat model of Parkinson＇ s disease and the mechanism. Methods Wistar female rats were ovariectomized and treated with vehicle or 17-βestradiol （1μg/5μl） intracerebroventricularly after unilateral injection of 6-OHDA into the medial forebrain bundle （MFB）. The changes of apomorphine-induced rotational behavior, tyrosine hydroxylase （TH） gene expression and iron contents in substantia nigra （SN）, DA and its metabolite contents in striatum were detected. Results 17-β estradiol treatment could ameliorate the rat＇ s rotational behavior induced by apomorphine compared to the PD model rats （ P 〈 0.05）. 17-βestradiol treatment could prevent the 6-OHDA-induced decrease of TH gene expression in the ipsilateral SN compared to the 6-OHDA group （ P 〈 0.01 ）. The DA, DOPAC and HVA levels in the striatum of the injured side of PD rats were significantly decreased compared with the intact side （ P 〈 0.01 ）. 17-β estradiol treatment could increase DA and its contents of metabolites in the injured side of striatum compared to the 6-OHDA group （ P 〈0.01 ）. Using Perls＇ iron staining, we also found that 17-βestradiol treatment could reverse the increase of iron staining in the ipsilateral SN compared to the 6-OHDA group （ P 〈 0.01 ）. Conclusion Estrogen has neuroprotective effect on the dopaminergic neurons in the 6-OHDA induced rat model of PD. The mechanism may be related to the decrease of iron overload.