有机磷化合物诱导母鸡迟发性神经毒性机制研究

发布时间：2019-01-11 09:28

【摘要】：有机磷化合物(organophosphorus compounds,OPs)是一类用途广泛的工业品,主要用做农药、增塑剂、阻燃剂、油料添加剂、润滑剂以及神经毒剂等。许多OPs还能在人体和敏感动物诱发迟发性神经毒性(organophosphate ester induced delayed neurotoxcity,OPIDN)或称为有机磷化合物引起的迟发性多发性神经病(organophosphate ester induced delayed polyneuropathy,OPIDP)。OPIDN的特征是在接触有机磷毒物到出现中枢.周围神经毒性症状有1～3周的潜伏期,表现为肌肉运动不协调、共济失调、痉挛强直及无力瘫痪。瘫痪多发生于下肢,逐渐影响上肢。OPIDN组织病理学上表现为脊髓和外周神经轴突的节间肿胀及退行性变,以及随之发生在长的粗大周围神经远端和脊髓感觉和运动传导束的髓鞘瓦氏变性。周围神经的损伤先于脊髓损伤。超微结构观察到肿胀的轴索内充满积聚的神经丝、微管、囊泡性结构及增生的滑面内质网。随后表现为神经丝成簇状及消失。尽管许多工作致力于OPIDN的研究,但其发病机制尚不清楚。基于OPIDN超微结构的观察和组织病理学的改变,为进一步探讨OPIDN发生的分子机制,我们选用了目前我国消耗量最大的农药甲胺磷及OPIDN经典诱导剂磷酸三邻甲苯酯(tri-ortho-cresyl phosphate,TOCP)作为受试物。甲胺磷和TOCP分别经皮下和经口途径诱发母鸡OPIDN;通过形态学观察、Western blotting、反转录聚合酶链式反应(reverse transcription polymerase chain reaction,RT-PCR)指标观察了甲胺磷诱发OPIDN后第2、10、23d及给予TOCP后第21d时周围神经超微结构的变化;检测了甲胺磷和TOCP对大脑、脊髓、坐骨神经中细胞骨架蛋白包括高分子量神经丝(high molecular weight neurofilament,NF-H),中分子量神经丝(middle molecular weight neurofilament,NF-M)以及低分子量神经丝(low molecular weight neurofilament,NF-L)、微管蛋白α-tubulin和β-tubulin、微丝肌动蛋白β-actin含量的动态影响;检测了大脑和脊髓中以上各
[Abstract]:Organophosphorus compounds (organophosphorus compounds,OPs) are widely used as industrial products, mainly used as pesticides, plasticizers, flame retardants, oil additives, lubricants and nerve agents. Many OPs can also induce delayed neurotoxic (organophosphate ester induced delayed neurotoxcity,OPIDN in humans and sensitive animals, or (organophosphate ester induced delayed polyneuropathy, caused by organophosphorus compounds. OPIDP). OPIDN is characterized by exposure to organophosphorus poison to the center of occurrence. The symptoms of peripheral neurotoxicity have a latent period of 1 to 3 weeks, which are characterized by muscle disharmony, ataxia, spasm and paralysis. Paralysis occurs in the lower extremities and gradually affects the upper extremity. The histopathology of OPIDN is characterized by swelling and degeneration of the internodes of the spinal cord and peripheral nerve axons. And subsequently myelin vaginosis occurs at the distal end of the long thick peripheral nerve and the sensory and motor conduction tracts of the spinal cord. Peripheral nerve injury precedes spinal cord injury. The swollen axons were observed to be filled with accumulated neurofilament, microtubule, vesicular structure and proliferative smooth endoplasmic reticulum. Then the neurofilament appeared in clusters and disappeared. Although much work has been devoted to the study of OPIDN, its pathogenesis remains unclear. Based on the ultrastructural observation of OPIDN and histopathological changes, in order to further study the molecular mechanism of OPIDN, we selected methamidophos, the most consumed pesticide in China, and tri-ortho-cresyl phosphate, the classical inducer of OPIDN. TOCP) as a subject. Induction of OPIDN; in hens by methamidophos and TOCP via subcutaneous and oral routes, respectively The ultrastructure of peripheral nerve was observed by morphological observation of, Western blotting, reverse transcriptase polymerase chain reaction (reverse transcription polymerase chain reaction,RT-PCR) on the 2nd day 1023 d after methamidophos induction of OPIDN and 21 d after TOCP administration. The effects of methamidophos and TOCP on cytoskeletal proteins including high molecular weight neurofilament (high molecular weight neurofilament,NF-H), middle molecular weight neurofilament (middle molecular weight neurofilament,) in the brain, spinal cord and sciatic nerve were detected. NF-M), low molecular weight neurofilament (low molecular weight neurofilament,NF-L), tubulin 伪-tubulin and 尾-tubulin, microfilament actin 尾-actin; Examined the above in the brain and spinal cord.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363

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