外源性犬尿喹啉酸对黑质多巴胺能神经元损伤保护作用的实验研究

Experimental study on protecting nigral dopamine neurons by extrogeneous kynurenic acid

  • 摘要: 目的: 观察评价预先应用谷氨酸(Glu)受体拮抗剂犬尿喹啉酸(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1 0只,应用江湾I型C立体定向仪,在单侧黑质致密部(SNc)及中脑被盖腹侧部(VTA),A组注射生理盐水,B组注射KYNA,C组注射KYNA和6-OHDA,KYNA先于6-OHDA 0 5h,D组注射6-OHDA。注射药物3d后,进行症状观察,2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TH阳性细胞及TH阳性纤维着色情况,实验数据分别采用方差分析以及秩和检验进行统计分析。结果: 正常黑质细胞体形较大,富含黑色素颗粒,可见尼氏体。数据统计分析结果提示B组与A组之间无显著影响,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: 外源性谷氨酸受体拮抗剂KYNA通过阻滞Glu受体能减轻6-OHDA诱导的黑质DA能神经元毒性损害。

     

    Abstract: Objective: To verify and evaluate the protective function of KYNA on the SNc dopaminergic cell bodies and fibres,which is microinjected thirty minutes prior to 6-OHDA. Methods: A total 40 adult female SD rats in 4groups (each of the 4groups consisting of 10 rats).GroupA,B,C,D received,respectively,a unilateral microinjection of normal saline,KYNA, KYNA+6-OHDA or 6-OHDA,into the left ventral tegmental area(VTA) and SNc.T wo weeks later,the changes of tyrosine hydroxylase-positive neurons in SNc and dopaminergic fiber in VTA were investigated in immunocytochemical methods. Data were reported as X S.Statistical significance levels were calculated by using Analysis of Variance and Rank Test. Results: In the third day after injection,the ethologic observation was performed following motivation by apomorphine. Group A and B have no symptom.Group C was significantly improved than group D.The number of T H-positive cells in group A,B,C significantly increase in comparison with the group D (P<0.01).Application of KYNA prior to 6-OHDA produced a significant increase of T H-positive fiberic density than group D around the injection sites in VTA. Conclusion: These data indicate that the early application of Glu receptor antagonist KYNA may decrease neurotoxic damage of 6-OHDA on nigral DA neurons.

     

/

返回文章
返回