【作者】 傅强；

【导师】 廖林川；

【作者基本信息】 四川大学 ， 法医学， 2007， 硕士

【摘要】 毒鼠强是一种含氮杂环类灭鼠药，其中毒剂量小，外观无色无味，且性质稳定，易因误食引起中毒，也被用作自杀或被犯罪分子利用，其致死率高。目前的研究多集中于毒鼠强中毒的临床表现及对症治疗等，有关基础性研究相对较少，因此，其毒理作用机制尚未完全阐明。本研究旨在探索毒鼠强中毒大鼠器官组织发生的病理改变与其中毒鼠强含量之间的关系：毒鼠强中毒大鼠器官组织发生的病理改变与中毒时间之间的关系，从而为揭示毒鼠强中毒的毒性机制，进一步诊治毒鼠强中毒提供科学依据，也为毒鼠强中毒的法医学鉴定提供参考。为了测定血液和组织中的毒鼠强含量，经过对萃取条件进行摸索及色谱条件的优化，本研究建立了生物检材中毒鼠强的分析方法。用苯作为萃取溶剂，运用GC-TSD作为检测手段。其色谱条件如下：分析仪器为VARIAN CP 3800，采用涂层为二甲基硅氧烷的CP-Sil5CB非极性熔融石英毛细管色谱柱(30m×0．25mm×0．25μm)，柱温程序100℃(?)210℃(2min)(?)→280℃(3min)，进样口温度280℃，TSD检测器温度300℃，载气为氮气，流速1mL／min，以与对照品的保留时间比对作为定性依据，用外标法定量。本研究选用健康SD大鼠作为研究动物。将实验动物随机分成五个实验组和一个对照组。一部分实验组大鼠用不同剂量毒鼠强进行染毒，于相同时间处死；另一部分实验组大鼠用相同剂量毒鼠强进行染毒，于不同时间处死。对照组大鼠灌服生理盐水作空白对照。采集各组大鼠的血液、心脏、肝脏和脑，用所建方法对染毒组大鼠器官组织中的毒鼠强含量进行测定，并运用多聚甲醛和戊二醛混合固定液对各组动物脏器进行固定，分别用光学显微镜和透射电镜对染毒大鼠器官组织发生的病理变化进行了观察，以考察毒鼠强染毒大鼠器官组织发生的病理改变与相应器官组织中的毒鼠强含量之间的关系和毒鼠强染毒大鼠器官组织发生的病理改变与中毒时间之间的关系。通过光镜观察发现，毒鼠强对染毒大鼠的脑干、心脏和肝脏均有一定损伤，且无明显性别差异。毒鼠强对心脏的损伤程度与毒鼠强的含量和中毒时间有一定的相关性，对脑干和肝脏的损伤程度与毒鼠强含量和中毒时间无明显相关性。通过电镜观察发现，脑干神经细胞内线粒体轻度扩张水肿、核糖体减少、胶质细胞基本正常，可见较为明显的神经纤维髓鞘脱失病变。毒鼠强引起的脑干神经纤维髓鞘脱失病变程度与脑组织中毒鼠强的含量和中毒时间均呈正相关，脑组织中毒鼠强的含量越高，中毒时间越长，脑干神经纤维脱髓鞘病变越严重。本课题建立了生物检材中毒鼠强的分析方法，首次研究了毒鼠强染毒大鼠器官组织发生的病理改变与相应器官组织中的毒鼠强含量和中毒时间之间的关系。为毒鼠强中毒机制的深入研究提供了重要参考，为毒鼠强中毒的诊治积累了资料，为毒鼠强中毒的法医学鉴定提供了参考。更多还原

【Abstract】 Tetramine is a kind of azacyclo-rodenticide with a small toxic dosage. Tetramine is a colorless, tasteless and stable substance. Poisoning which caused by taking it by mistake is very common as well as in suicide or criminal cases. It is of a high death rate. At present, there are many researches on the clinical manifestation and the symptomatic treatment of people poisoned by tetramine, while there are few the foundation research references of its toxic mechanism. Therefore, its toxic mechanism hasn’t been elucidated. This research aimed at showing the pathological change of poisoned rat and the relationship between the tetramine quantity and poisoning time, providing science basis for revealing its toxic mechanism, for the clinical diagnosis and treatment of people poisoned by tetramine, providing reference for medicolegal expertise of cases caused by tetramine.In order to determine the tetramine concentration in blood and tissues, after inspecting some extracting solvent and optimizing chromatographic condition. The analytical method for tetramine in biomaterial was established in this study. Tetramine was extracted by benzene and determined by GC-TSD which will describe as follow. A VARIAN CP 3800 gas chromatography equipped with a nitrogen/phosphorus detector (TSD) was introduced in this paper to determinate tetramine. Compounds were separated on a CP-Sil5CB fused silica capillary column coated with dimethyl siloxane thickness 0.25μm 30m×0.25mm i.d. The column temperature program was set as follows: 100℃(?) 210℃(2min) (?)280℃(3min). Nitrogen gas was used as the carrier gas, at a flow rate of 1mL/min.We used the retention time of tetramine standard for qualitation, external reference method for quantitation.In this study, we used healthy SD-rats as experimental animal, divided them to five and a control group at random. The rats in the experimental groups were used for poisoning experiment. Some of them were poisoned with different dosage then killed at the same time. Others were poisoned with the same dosage then killed at different time. The control group was given physiologic saline as blank. We collected the blood, heart, liver and brain of every rat, determined tetramine in these samples of experimental groups, used the solution consisted of paraformaldehyde and glutaraldehyde to fix tissues, applied light microscope and transmission electron microscope to observe pathological changes. In the end, we investigated the pathological change and the relationship between tetramine quantity and the poisoning time.The pathological change observed by the light microscope show that teteamine could injure the brainstem, heart and liver of poisoned rats without obvious sex differences. The degree of heart injury did have some thing to do with tetramine quantity and the poisoning time. While the degree of brainstem and liver injury did not have distinct dependablity relativity to tetramine quantity and the poisoning time.The pathological change observed by the transmission electron microscope show that there are dropsical cytochondria, reduction of ribosomes, normal gliacyte and neurofibra myelinolysis. The neurofibra myelinolysis caused by tetramine had a positive correlation to tetramine quantity and the poisoning time. The higher concentration of tetramine in brain tissue and longer poisoning time, would cause a worse neurofibra myelinolysis.In this study, we established the method for detecting tetramine in biomaterial, investigated the pathological change and the relationship between tetramine quantity and the poisoning time. The results could provide reference for further study on toxic mechanism of tetramine and offer valuable gist for the clinical diagnosis and treatment of people poisoned by tetramine, providing reference for medicolegal expertise of cases caused by tetamine.更多还原