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目的 观察评价预先应用谷氨酸 (Glu)受体拮抗剂kynurenicacid(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 4 0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 30min ,D组注射 6 OHDA。注射药物 3d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 .0 5。实验组C与A、B、D组比较均有显著性差异 ,P <0 .0 1。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。
Objective To evaluate the protective effect of kynurenicacid (KYNA), a glutamate receptor antagonist, on dopaminergic neurons and nerve fiber damage in substantia nigra. Methods Female Sprague-Dawley rats were randomly divided into 4 groups with 10 rats in each group. The rats were anesthetized with Jiangwan Type I C Stereotaxy instrument, and the unilateral substantia nigra pars compacta and midbrain were ventrally covered. Brine was injected into group B, KYNA was injected into group B, KYNA and 6-OHDA were injected into group C, KYNA was pre-incubated with 6-OHDA for 30 min, and group D was injected with 6-OHDA. After injection of the drug for 3 days, the symptoms were observed and the rats were sacrificed after 4 weeks. The morphological features of nigral cells were observed by HE staining. Immunohistochemical staining was used to observe the staining of tyrosine hydroxylase (TH) positive cells and TH positive fibers by frozen sections. Results Normal nodular cells larger shape, rich in melanin granules, visible Nisshin. TH staining results suggest no significant difference between group B and group A, P> 0. There was significant difference between experimental group C and A, B and D groups (P <0.01). Conclusion The exogenous Glu receptor antagonist KYNA can reduce the damage induced by 6 OHDA in substantia nigra DA neurons through blocking the Glu receptor for a certain period of time.