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[萘呋胺酯(LS129)对轴突生长的影响]

[Effect of naftidrofuryl (LS129) on axonal growth].

作者信息

Meininger V, Chaineau E, Soudière B

机构信息

Laboratoire d'Anatomie, Faculté de Médecine, Paris.

出版信息

Rev Neurol (Paris). 1994;150(2):115-22.

PMID:7863151
Abstract

The response of growing axons and microtubules to naftidrofuryl (LS 129) was investigated in vitro and in situ in the embryonic nervous system of mice. For this purpose, we used rotatory cultures of post-implanted embryos in a rat or human serum containing the compound combined with immunofluorescence using a tubulin-specific polyclonal antibody on high molecular weight polyethylene-glycol embedded semithin sections. We also analysed the protective effect of naftidrofuryl to treatment with vinka alkaloids using the same method. After culture in rat serum enriched with naftidrofuryl at concentration of 20 microM and above, we observed an increase of both the number of axonal profiles in semithin sections and of the number of microtubules per surface unit in electron micrographs. After culture in human serum obtained from an healthy volunteer after a unique intake of naftidrofuryl at 900 mg/j and above, we observed the same effect of an increasing of the number of axonal profiles in the tectal plate of mice embryos in semithin sections. These results suggest a promoting effect of naftidrofuryl on axonal growth and on microtubules' assembly. They suggest a therapeutic effect of this drug at daily doses of 900 mg/j. After culture in a rat serum enriched with naftidrofuryl at concentration of 20 microM, we observed a protective effect of this drug toward the disruption of axonal microtubules by vinka alkaloids. This effect seems rather specific since we did not observe the same protection toward the mitotic microtubules. These results suggest that naftidrofuryl could be used to prevent the neurological side effects of vinka alkaloids.

摘要

在小鼠胚胎神经系统中,对萘呋胺酯(LS 129)在体外和原位条件下对生长中的轴突和微管的反应进行了研究。为此,我们使用植入后胚胎在含有该化合物的大鼠或人血清中的旋转培养,并结合在高分子量聚乙二醇包埋的半薄切片上使用微管蛋白特异性多克隆抗体进行免疫荧光检测。我们还使用相同方法分析了萘呋胺酯对长春花生物碱治疗的保护作用。在富含浓度为20微摩尔及以上萘呋胺酯的大鼠血清中培养后,我们观察到半薄切片中轴突轮廓数量以及电子显微镜照片中每表面单位微管数量均增加。在一名健康志愿者单次摄入900毫克/天及以上萘呋胺酯后获得的人血清中培养后,我们在半薄切片中观察到小鼠胚胎顶盖板中轴突轮廓数量增加的相同效果。这些结果表明萘呋胺酯对轴突生长和微管组装具有促进作用。它们表明该药物在每日剂量为900毫克/天时有治疗效果。在富含浓度为20微摩尔萘呋胺酯的大鼠血清中培养后,我们观察到该药物对长春花生物碱破坏轴突微管具有保护作用。这种作用似乎相当特异,因为我们未观察到对有丝分裂微管的相同保护作用。这些结果表明萘呋胺酯可用于预防长春花生物碱的神经学副作用。

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