CAJ | 학술논문

背景：接触有机磷化合物可导致迟发神经病的发生，然而因为迟发性神经病发生的确切机制不清楚而尚无有效的治疗方法。目的：构建磷酸三邻甲苯酯诱导鸡迟发性神经毒性模型并观察苯甲基磺酰氟预处理的影响。方法：将成年罗曼母鸡随机分为2个磷酸三邻甲苯酯染毒组，苯甲基磺酰氟预处理组和对照组。其中磷酸三邻甲苯酯染毒组浓度分别为1000 mg/kg和750 mg/kg，均一次性灌胃；苯甲基磺酰氟预处理组先将苯甲基磺酰氟按40 mg/kg剂量给鸡皮下注射，24 h后，再经灌胃一次性给鸡1000 mg/kg的磷酸三邻甲苯酯；而对照组则给予等量生理盐水。使用6分制来评价迟发性神经病临床症状并记录鸡的体质量变化。在染毒第5，21天分别断头处死鸡，制备电镜切片并于电镜下观察。结果与结论：磷酸三邻甲苯酯染毒后鸡临床症状随着时间的延长而渐进性加重(P <0.05)，体质量显著降低(P <0.05)，但苯甲基磺酰氟预处理组鸡与对照组鸡实验期间则无任何迟发性神经病异常表现和体质量变化。磷酸三邻甲苯酯组染毒5 d后，发现一些线粒体有轻微肿胀，轴突内微丝微管排列发生可疑改变，但是其他细胞器没有明显异常改变。磷酸三邻甲苯酯组染毒21 d后，脑神经元退行性改变明显，内质网肿胀，线粒体异常改变，细胞骨架排列紊乱。1000 mg/kg的磷酸三邻甲苯酯为最佳染毒剂量。结果显示，实验成功建立了磷酸三邻甲苯酯诱导鸡迟发性神经毒性模型和苯甲基磺酰氟预处理模型，苯甲基磺酰氟预处理能明显改善磷酸三邻甲苯酯染毒后鸡迟发性神经病的临床症状和病理改变。
배경：접촉유궤린화합물가도치지발신경병적발생，연이인위지발성신경병발생적학절궤제불청초이상무유효적치료방법。목적：구건린산삼린갑분지유도계지발성신경독성모형병관찰분갑기광선불예처리적영향。방법：장성년라만모계수궤분위2개린산삼린갑분지염독조，분갑기광선불예처리조화대조조。기중린산삼린갑분지염독조농도분별위1000 mg/kg화750 mg/kg，균일차성관위；분갑기광선불예처리조선장분갑기광선불안40 mg/kg제량급계피하주사，24 h후，재경관위일차성급계1000 mg/kg적린산삼린갑분지；이대조조칙급여등량생리염수。사용6분제래평개지발성신경병림상증상병기록계적체질량변화。재염독제5，21천분별단두처사계，제비전경절편병우전경하관찰。결과여결론：린산삼린갑분지염독후계림상증상수착시간적연장이점진성가중(P <0.05)，체질량현저강저(P <0.05)，단분갑기광선불예처리조계여대조조계실험기간칙무임하지발성신경병이상표현화체질량변화。린산삼린갑분지조염독5 d후，발현일사선립체유경미종창，축돌내미사미관배렬발생가의개변，단시기타세포기몰유명현이상개변。린산삼린갑분지조염독21 d후，뇌신경원퇴행성개변명현，내질망종창，선립체이상개변，세포골가배렬문란。1000 mg/kg적린산삼린갑분지위최가염독제량。결과현시，실험성공건립료린산삼린갑분지유도계지발성신경독성모형화분갑기광선불예처리모형，분갑기광선불예처리능명현개선린산삼린갑분지염독후계지발성신경병적림상증상화병리개변。
BACKGROUND:Although incidents of organophosphorus poisoning-induced delayed neuropathy (OPIDN) have been documented for over a century, the molecular mechanisms underlying the axonopathy remain poorly understood. Therefore, OPIDN treatment has been increasingly concerned. OBJECTIVE:To construct the OPIDN hen model induced by triorthocresyl phosphate (TOCP) and to explore the effect of phenylmethylsulfonyl fluoride (PMSF) intervention. METHODS:Adult hens were randomly divided into four groups: two TOCP groups, a PMSF group and a control group. TOCP groups were treated with TOCP by gavage at a single dosage of 1 000 mg/kg and 750 mg/kg respectively; control group was given an equivalent volume of saline by gavage while hens in the PMSF group were subcutaneously injected with 40 mg/kg PMSF 24 hours after 1 000 mg/kg TOCP injection. OPIDN neurological signs were assessed by a six-point graded scale. The changes of the hen weight were recorded. The hens were kiled on day 5 and 21 post-dosing. The samples were cut into 50 nm thick sections and examined by transmission electron microscopy. RESULTS AND CONCLUSION:OPIDN neurological signs such as abnormal gaits progressed in severity with time (P < 0.05), and the hen weight was significantly decreased in TOCP groups (P < 0.05). However, no clinical signs of delayed neurotoxicity were observed in hens of the PMSF group and the control group during the experiment period. The mild mitochondrial sweling and the fragmentation of microfilament and microtubule arrangement in axons were observed on day 5 post-dosing, leaving the other organeles remained unchanged. On day 21, neuronal degeneration was apparent, including sweling of endoplasmic reticulum, abnormal change of mitochondria, and disordered arrangement of cytoskeleton. The optimal dose of TOCP was 1 000 mg/kg. Experimental findings indicate that, OPIDN hen model induced by TOCP and PMSF intervention hen model were successfuly constructed. PMSF intervention significantly improved the pathologic changes and clinical symptoms of OPIDN induced by TOCP in hens.