盐酸地芬尼多在中毒大鼠体内死后再分布的研究

发布时间：2018-05-21 02:33

本文选题：盐酸地芬尼多 + 死后分布　；参考：《山西医科大学》2006年硕士论文

【摘要】：目的 1．建立盐酸地芬尼多中毒死亡、死后再分布、死后弥散的动物模型，观察动物的中毒表现和死后各组织脏器的病理变化； 2．研究盐酸地芬尼多致死动物体内的死后分布和死后再分布，为盐酸地芬尼多中毒死亡案件的法医学鉴定提供科学依据； 3．研究盐酸地芬尼多在家兔体内的死后弥散特点，探讨死后再分布的可能机制。方法 1．动物模型及检材采集和处理 1．1 死后分布模型大鼠22只，分两组(1600mg／kg、800mg／kg。第1组6只，盐酸地芬尼多1600mg／kg灌胃。第2组16只，盐酸地芬尼多800mg／kg灌胃，观察4小时，未死者，颈椎脱臼致死。待呼吸和心跳全部消失时，迅速解剖大鼠，取脑、心、肺、肝、脾、肾、脑、胃和心血等组织脏器和体液，检测其中盐酸地芬尼多含量。 1．2 死后再分布模型大鼠30只，分别灌服盐酸地芬尼多800mg／kg，观察4小时，颈椎脱臼致死。待染毒大鼠呼吸和心跳全部消失后，立即分别置于室温下，分别于死后0，4，8，16，24，48，72小时提取大鼠的心血、心、肝、脾、肺、肾、脑、肌肉(左腿)和心血，，检测其中盐酸地芬尼多含量。 1．3 死后弥散动物模型 1．3．1 死后弥散家兔24只完全夹闭气管12分钟后，分别经灌胃管灌入盐酸地芬尼多400mg／kg，分别于灌胃后1、3、6、12、24、48、72、96小时各解剖3只，取材。 1．3．2 剂量对死后弥散影响家兔12只，分4组，完全夹闭气管12分钟后，分别经灌胃管灌入盐酸地芬尼多400mg／kg、200mg／kg、80mg／kg、40mg／kg，24小时后取材。 1．3．3 死后灌胃时间对死后弥散影响家兔12只，分4组，完全夹闭气管12分钟后0分钟、30分钟、60分钟、120分钟分别经灌胃灌入盐酸地芬尼多400mg／kg，24小时后取材。采取家兔的心、肝、脾、肺、肾、脑、肌肉、心血、外周血、胆汁和尿，检测其中盐酸地芬尼多含量。 2．病理观察取死后分布模型脑、心、肝、脾、肺、肾等组织，用4％甲醛固定，石蜡包埋，切片，HE染色，光镜观察。 3．盐酸地芬尼多检测方法样品匀浆后，加入内标，经酸、碱处理后，乙醚萃取，气相色谱和气相色谱-质谱联用检测，根据盐酸地芬尼多的特征离子峰、保留时间定性，工作曲线法定量。
[Abstract]:Purpose 1. The animal models of difenidol hydrochloride poisoning death, postmortem redistribution and postmortem dispersion were established to observe the toxic manifestations of animals and the pathological changes of organs after death. 2. To study the postmortem distribution and postmortem redistribution of difenidol hydrochloride in the body of lethal animals, and to provide scientific basis for forensic identification of difenidol hydrochloride poisoning death cases. 3. To study the diffusion characteristics of difenidol hydrochloride after death in rabbits and to explore the possible mechanism of postmortem redistribution. Method 1. Collection and treatment of animal models and samples 1.1 Twenty-two postmortem model rats were divided into two groups: 1600mg / kg, 800mg / kg. Group 1 (n = 6): Difenido hydrochloride (1600mg/kg) was administered intragastrically. In the second group, 16 rats were treated with Difenido 800mg/kg hydrochloride and observed for 4 hours. No one died of cervical dislocation. When the respiration and heartbeat disappeared, the rats were dissected quickly, and the tissues and body fluids of brain, heart, lung, liver, spleen, kidney, brain, stomach and heart blood were taken, and the content of difenidol hydrochloride was detected. 1.2 Thirty postmortem redistributed model rats were administrated with difenido hydrochloride 800 mg / kg for 4 hours, and the cervical vertebrae dislocated and died. When the rats' respiration and heartbeat disappeared, they were placed at room temperature respectively. The heart blood, heart, liver, spleen, lung, kidney, brain, muscle (left leg) and heart blood of the rats were extracted at 0 ~ (4) ~ 4 ~ 4 ~ (16) ~ (16) ~ (24) ~ 4 ~ (872) h after death, and the contents of difenidol hydrochloride were measured. 1.3 diffuse postmortem animal models 1.3.1 after 12 minutes of complete clamping of trachea, 24 rabbits were perfused with difenido hydrochloride 400 mg / kg, respectively. 1.3.2 effect of dose on postmortem dispersion Twelve rabbits were divided into 4 groups. The trachea was completely clamped for 12 minutes. After 12 minutes, the rabbits were perfused with Difenido hydrochloride 400 mg / kg / kg ~ (200 mg / kg) / kg ~ (80 mg / kg) / kg ~ (40 mg / kg) / kg for 24 hours respectively. 1.3.3 effect of postmortem gavage time on postmortem dispersion Twelve rabbits were divided into 4 groups. The trachea was completely clamped for 12 minutes, 30 minutes and 60 minutes and 120 minutes, respectively, by intragastric administration of Difenido hydrochloride 400 mg / kg 路kg ~ (-1) for 24 hours. The heart, liver, spleen, lung, kidney, brain, muscle, heart blood, peripheral blood, bile and urine of rabbits were measured. 2. Pathological changes of brain, heart, liver, spleen, lung and kidney were observed, fixed with 4% formaldehyde, embedded in paraffin, stained with HE in sections and observed under light microscope. 3. After homogenization of Difenidol hydrochloride sample, internal standard was added, after acid and alkali treatment, ether extraction, gas chromatography and gas chromatography-mass spectrometry were used to determine the retention time. Work curve measurement.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：D919

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