NEURAL-TUBE DEFECTS CAUSED BY LOCAL-ANESTHETICS IN EARLY CHICK-EMBRYOS
NEURAL-TUBE DEFECTS CAUSED BY LOCAL-ANESTHETICS IN EARLY CHICK-EMBRYOS
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DOI：
10.1002/tera.1420310114
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发表时间：
1985-01-01
期刊：
影响因子：
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通讯作者：
NAGELE, RG
中科院分区：
文献类型：
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作者：
LEE, H;NAGELE, RG
研究了局麻药(盐酸氯胺酮、利多卡因、普鲁卡因和丁卡因)对8期(4体型)鸡胚胎的影响。总体而言，胚胎在孵化的前6小时内对药物的反应与剂量有关。浓度为500微克/毫升(apprx.2 mm或更高为胚胎致死性，而100-200微克/毫升(0.1-0.8 mm)优先抑制神经皱褶的抬高。后一种效应在治疗后3h内即可检测到，并且很容易逆转。在测试的4种局麻药中，丁卡因在任何给定剂量下都是最有效的。与对照组相比，缺陷神经上皮中的细胞伸长较小，顶端(管腔)表面更光滑，微丝束更细，肌动蛋白特异性荧光强度更低。局麻药(100-200微克/毫升)对第8期鸡胚的作用与细胞松驰素D(0.05微克/毫升)、秋水仙碱(1.微克/毫升)或离子载体A23187(25微克/毫升)的效果不同，尽管所有处理都有神经管缺陷。局麻药通过对发育中的神经上皮细胞中微丝的组织和功能的破坏作用来抑制神经管的关闭。
The effects of local anesthetics (ketamine HCl, lidocaine HCl, procaine HCl and tetracaine HCl) on stage 8 (4-somite) chick embryos were investigated. In general, embryos responded to drug treatment in a dose related manner during the first 6 h of incubation. Concentrations of 500 .mu.g/ml (.apprx. 2 mM) or higher were embryolethal, whereas 100-200 .mu.g/ml (0.1-0.8 mM) preferentially inhibited elevation of neural folds. The latter effect was detectable within 3 h of treatment and was readily reversible. Tetracaine was the most potent among the 4 local anesthetics tested at any given dose. Compared to controls, cells in the defective neuroepithelium were less elongated and exhibited smoother apical (luminal) surfaces, thinner microfilament bundles and less intense actin-specific fluorescence. The effects of local anesthetics (100-200 .mu.g/ml) on stage 8 chick embryos were not identical to those of cytochalasin D (0.05 .mu.g/ml), colchicine (1 .mu.g/ml) or ionophore A23187 (25 .mu.g/ml), although all treatments produced neural tube defects. Local anesthetics inhibit closure of the neural tube through their disruptive action on the organization and function of microfilaments in developing neuroepithelical cells.