【摘要】：有機磷化合物(organophosphorus compounds,OPs)是一類用途廣泛的工業(yè)品,主要用做農(nóng)藥、增塑劑、阻燃劑、油料添加劑、潤滑劑以及神經(jīng)毒劑等。許多OPs還能在人體和敏感動物誘發(fā)遲發(fā)性神經(jīng)毒性(organophosphate ester induced delayed neurotoxcity,OPIDN)或稱為有機磷化合物引起的遲發(fā)性多發(fā)性神經(jīng)病(organophosphate ester induced delayed polyneuropathy,OPIDP)。OPIDN的特征是在接觸有機磷毒物到出現(xiàn)中樞.周圍神經(jīng)毒性癥狀有1～3周的潛伏期,表現(xiàn)為肌肉運動不協(xié)調(diào)、共濟失調(diào)、痙攣強直及無力癱瘓。癱瘓多發(fā)生于下肢,逐漸影響上肢。OPIDN組織病理學上表現(xiàn)為脊髓和外周神經(jīng)軸突的節(jié)間腫脹及退行性變,以及隨之發(fā)生在長的粗大周圍神經(jīng)遠端和脊髓感覺和運動傳導束的髓鞘瓦氏變性。周圍神經(jīng)的損傷先于脊髓損傷。超微結(jié)構(gòu)觀察到腫脹的軸索內(nèi)充滿積聚的神經(jīng)絲、微管、囊泡性結(jié)構(gòu)及增生的滑面內(nèi)質(zhì)網(wǎng)。隨后表現(xiàn)為神經(jīng)絲成簇狀及消失。盡管許多工作致力于OPIDN的研究,但其發(fā)病機制尚不清楚。基于OPIDN超微結(jié)構(gòu)的觀察和組織病理學的改變,為進一步探討OPIDN發(fā)生的分子機制,我們選用了目前我國消耗量最大的農(nóng)藥甲胺磷及OPIDN經(jīng)典誘導劑磷酸三鄰甲苯酯(tri-ortho-cresyl phosphate,TOCP)作為受試物。甲胺磷和TOCP分別經(jīng)皮下和經(jīng)口途徑誘發(fā)母雞OPIDN;通過形態(tài)學觀察、Western blotting、反轉(zhuǎn)錄聚合酶鏈式反應(yīng)(reverse transcription polymerase chain reaction,RT-PCR)指標觀察了甲胺磷誘發(fā)OPIDN后第2、10、23d及給予TOCP后第21d時周圍神經(jīng)超微結(jié)構(gòu)的變化;檢測了甲胺磷和TOCP對大腦、脊髓、坐骨神經(jīng)中細胞骨架蛋白包括高分子量神經(jīng)絲(high molecular weight neurofilament,NF-H),中分子量神經(jīng)絲(middle molecular weight neurofilament,NF-M)以及低分子量神經(jīng)絲(low molecular weight neurofilament,NF-L)、微管蛋白α-tubulin和β-tubulin、微絲肌動蛋白β-actin含量的動態(tài)影響;檢測了大腦和脊髓中以上各
[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 偽-tubulin and 尾-tubulin, microfilament actin 尾-actin; Examined the above in the brain and spinal cord.
【學位授予單位】：山東大學
【學位級別】：博士
【學位授予年份】：2005
【分類號】：R363

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