摘要
莠去津(Atrazine, ATR)是一类常用的禾本科杂草和阔叶草类除草剂,具有长期广泛的环境毒性。ATR属于内分泌干扰物(Endocrine-disrupting chemicals, EDCs),它的毒性危害主要体现在诱发生殖器官畸形、致癌性、发育迟缓、免疫力低下等方面。目前关于ATR对神经系统的毒理作用的认识仅限于它干扰丘脑—垂体轴的中枢神经内分泌调控。本文以斑马鱼胚胎和幼鱼作为实验对象,通过行为学、组织细胞形态学和乙酰胆碱酯酶(AChE)活性定量分析,研究了不同ATR浓度急性处理的胚胎和幼鱼的生理生化指标的变化,以及这些变化对神经信号整合和行为的影响。研究发现,ATR可以削弱幼鱼的游泳活力、削弱对整合能力要求较高的逃避行为。这些行为指标改变的组织学基础是ATR诱导的肌节发育不良和运动中枢内纤维束减少。白肌肌纤维的数量和排列方式受ATR影响显著,肌节长度缩短。进一步分析发现,ATR处理的幼鱼体内AChE活性水平被下调,可以指示肌肉的神经支配效率被削弱。有趣的是,ATR处理的胚胎体内AChE活性则被上调；与此同时,胚胎体内主要表达AChE的初级感觉神经元(Rohon-Beard cells)的生理性凋亡减少。这些现象表明,ATR通过干扰感觉神经元的发育过程、肌肉的神经支配以及神经信号的上下行传导过程来干扰斑马鱼的运动整合能力。这一结果对于全面认识ATR的环境风险和评价其毒性危害具有重要意义。
Atrazine (2-chloro-4-ethylamino-6-isopropylamine-s-triazine, ATR) is a widely used selective herbicide to control broadleaf weeds and gramineous grasses. It has intensified pollution of the environment and maintains toxicity on long-time scale. ATR is a kind of endocrine-disrupting chemicals, inducing malformation of reproductive system, carcinogenesis, adolescence delay, weakness of immunity and others. Despite it disrupts neuroendocrine regulation of thalamus-pituitary axis, little is known about its effects on neural system. In the dissertation, zebrafish embryos and larvae had worked as bio-monitor to discover physiological and biochemical changes of embryos and larvae acute treated with ATR as well as neural integration and behavior affected by these changes. By quantitative analysis of behavior, histological and cellular morphology, AChE activity, the study observed that ATR weakened swimming activity of larvae and impaired escape behavior. The behavioral changes caused by ATR-induced hypogenetic axial muscles and by reduced injective fasciculi in hindbrain and spinal cord. Number and arrangement of myofibers (esp. white muscle myofibers) were significantly influenced, and trunk myotomes shortened. Corresponding to this, AChE activity level has been down-regulated in ATR treated larvae. It marked that efficiency of muscle innervation has been crippled. Interestingly, AChE activity has been up-regulated in ATR-treated larvae. A parallel phenomenon shown that embryonic primary sensory neurons (Rohon-Beard cells), principally expressing AChE in embryos, survived the physiological apoptosis. All above indicate that ATR disrupts maturation of primary sensory neurons and innervation of axial muscle and injection of upper/lower motor neuron, and causes to harm integration of locomotion. The results play important role to entirely understand environmental risks and to estimate neurotoxic damage of ATR.
引文
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