CAJ | 학술논문

背景:帕金森病治疗方法有多种,多巴胺替代疗法、外科靶点永久毁损、脑深部核团高频电刺激术、脑移植和基因治疗.这些外科及药物治疗都有一些不足及难以弥补的缺陷,国内外学者将多巴胺能神经元保护剂的研究和应用提到了重要位置.目的:观察评价预先应用谷氨酸受体拮抗剂犬尿烯酸对黑质多巴胺能神经元及神经传导纤维损伤的保护性作用.设计:采用随机对照单盲实验研究.地点和材料:研究地点为解放军总医院神经外科实验室;实验动物选取雌性SD大鼠(取自解放军总医院动物饲养室,40只,体质量210～240 g,平均228 g).干预: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,分别注射生理盐水,犬尿烯酸,犬尿烯酸加6-羟多巴胺,6-羟多巴胺.注射药物3 d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,冷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.主要观察指标:切片HE染色观察黑质细胞的形态特点,冷冻切片免疫组化特殊染色观察TH阳性细胞数及TH阳性纤维着色等级.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犬尿烯酸组与生理盐水组之间差异无显著性意义(P＞0.05).实验组犬尿烯酸加6-羟多巴胺组与其他3组比较均差异有显著性意义(P＜0.01).结论:外源性谷氨酸受体拮抗剂犬尿烯酸(kynurenic acid,KYNA)通过阻滞Glu受体能减轻6-羟多巴胺诱导的黑质多巴胺能神经元毒性损害.
배경:파금삼병치료방법유다충,다파알체대요법、외과파점영구훼손、뇌심부핵단고빈전자격술、뇌이식화기인치료.저사외과급약물치료도유일사불족급난이미보적결함,국내외학자장다파알능신경원보호제적연구화응용제도료중요위치.목적:관찰평개예선응용곡안산수체길항제견뇨희산대흑질다파알능신경원급신경전도섬유손상적보호성작용.설계:채용수궤대조단맹실험연구.지점화재료:연구지점위해방군총의원신경외과실험실;실험동물선취자성SD대서(취자해방군총의원동물사양실,40지,체질량210～240 g,평균228 g).간예:자성SD대서40지,수궤분위4조,매조10지,응용강만Ⅰ형C입체정향의,재단측흑질치밀부급중뇌피개복측부,분별주사생리염수,견뇨희산,견뇨희산가6-간다파알,6-간다파알.주사약물3 d후,진행증상관찰,2주후처사대서.절편HE염색관찰흑질세포적형태특점,냉동절편면역조화특수염색관찰TH양성세포급TH양성섬유착색정황,실험수거분별채용방차분석이급질화검험진행통계분석.주요관찰지표:절편HE염색관찰흑질세포적형태특점,냉동절편면역조화특수염색관찰TH양성세포수급TH양성섬유착색등급.결과:정상흑질세포체형교대,부함흑색소과립,가견니씨체.수거통계분석결과제시견뇨희산조여생리염수조지간차이무현저성의의(P＞0.05).실험조견뇨희산가6-간다파알조여기타3조비교균차이유현저성의의(P＜0.01).결론:외원성곡안산수체길항제견뇨희산(kynurenic acid,KYNA)통과조체Glu수체능감경6-간다파알유도적흑질다파알능신경원독성손해.
BACKGROUND: There are many therapies in the treatment of Parkinson' s Disease(PD), for example, dopamine replacement, surgical permanent destroy in target point, high frequency electric stimulation in cerebral deep nuclei, brain transplantation and gene therapy. All these surgical and medical treatments have some disadvantages and unredeemable shortcomings. Therefore, national and international scholars pay more attentions to the researches and applications on the protective agents of dopaminergic neuron.OBJECTIVE: To observe and evaluate the protective reaction of the pre-application of the kynurenic acid, an antagonist of glutamicacid receptor, on the injury of dopaminergic neuron and nervous conductive fibres in substantia nigra ( SN ).DESIGN: A randomized controlled single blind study.SETTING and MATERIALS: Settings: Laboratory of the department of neurosurgery in General Hospital of PLA; Experimental animals: Forty female SD rats obtained from animal feeding department of General Hospital of Chinese PLA with a body mass from 210 g to 240 g(mean of 228 g) were selected.INTERVENTIONS: Forty female SD rats were randomly allocated into 4groups with 10 rats each. NS, kynurenic acid, kynurenic acid and 6-hydroxydopamine (6-OHDA), and 6-OHDA were injected respectively into one side of pars compacta of SN(SNpc) and ventral part of tegnentam in midbrain(VTA) by Jiangwan-I model C solid orientation analyser. Symptoms were observed after 3-day of injection. Rats were executed after 2weeks. Cerebral slices were stained by HE staining to observe the morphological features of SN cells. Frozen slices were stained by immunohistochemical specific staining to observe TH-IR(immune reactive) positive cell and the staining condition of TH-IR positive fibres. Experiment data were statistically analysed by analysis of variance and rank test.MAIN OUTCOME MEASURES: The morphological features of SN cells in slices were observed under HE staining, the numbers of TH-IR positive cells and the stain rank of TH-IR positive fibre in frozen slices were under immunohistochemical specific staining.RESULTS: The shape of normal SN cells was comparatively bigger containing rich melanin granules, in which Nissl bodies could be seen. The results of statistical analysis indicated that there was no significant difference between kynurenic acid group and NS group( P ＞ 0.05); and there were significant differences between kynurenic acid + 6-OHDA group and other three groups(P＜0. 01).CONCLUSION: Exogenic kynurenic acid, an antagonist of glutamicacid receptor, can relieve the neurotoxicity in dopaminergic neuron of SN induced by 6-OHDA through blocking the receptor of glutamicacid.