外源性kynurenic acid对大鼠黑质多巴胺能神经元损伤的保护作用研究

目的观察评价预先应用谷氨酸(Glu)受体拮抗剂kynurenic acid(KYNA)对黑质多巴胺(DA)能神经元及神经传导纤维损伤的保护性作用. 方法雌性SD大鼠40只,随机分为4组,每组10只,应用江湾I型C立体定向仪,在单侧黑质致密部及中脑被盖腹侧部, A组注射生理盐水,B组注射KYNA,C组注射KYNA和6-羟基多巴胺(6-OHDA), KYNA先于6-OHDA 30 min, D组注射6-OHDA.注射药物3 d后,进行症状观察,4周后处死大鼠.切片HE染色观察黑质细胞的形态特点,冰冻切片免疫组化特殊染色观察酪氨酸羟化酶(TH)阳性细胞及TH阳性纤维着色情况.结果正常黑质细胞体形较大,富含黑色素颗粒,可见尼氏体.TH着色结果提示B组与A组之间无显著差异,P>0.05.实验组C与A、B、D组比较均有显著性差异,P<0.01.结论外源性Glu受体拮抗剂KYNA通过阻滞Glu受体一定时间阶段内能减轻6-OHDA诱导的黑质DA能神经元毒性损害.

Experimental study on protection of extrogeneous kynurenic acid on rat nigral dopamine neurons

Objective To verify and evaluate the protective function of glutamine (Glu) receptor antagonist , kynurenic acid(KYNA), on the dopaminergic(DA) cell bodies and fibres of substantia nigra pars compacta. Methods A total of 40 adult female SD rats in 4 groups (each of 4 groups consisting of 10 rats), GroupA, B, C, D received, respectively , an unilateral microinjection of normal saline, KYNA, KYNA + 6 OHDA , which was microinjected thirty minutes prior to 6 hydroxydo pamine (6 OHDA),or 6 OHDA, into the left ventral tegmental area and substantia nigra pars compacta. Two weeks later, the change of tyrosine hydroxylase (TH) positive neurons in substantia nigra pars compacta and dopaminergic fiber in ventral tegmental area were investigated in immunocytochemical methods.Results In the third day after injection, the ethologic observation was performed following motivation by apomorphine. Group A and B had no symptom. Group C was significantly improved compared with group D. The number of TH positive cells in group A, B, C significantly increased in comparison with the group D( P <0.01). Application of KYNA prior to 6 OHDA produced more significant increase of TH positive fiberic density than group D around the injection sites in ventral tegmental area . Conclusion These data indicate that the early application of Glu receptor antagonist KYNA may decrease neurotoxic damage of 6 OHDA on nigral DA neurons.