吗啡类毒品中毒死者主要脏器内吗啡分布的研究

目的研究吗啡在人体脏器中的分布情况,筛选适于免疫组化方法检测吗啡的脏器。方法用免疫组化SP法对8例吗啡类毒品中毒死亡尸体脑、肾、心、肝等脏器中的吗啡进行定位和半定量观察。结果吗啡主要分布在某些实质细胞的胞浆内,肾脏和脑组织的吗啡含量高,不同器官、不同案例吗啡的分布情况差异较大。结论肾脏和脑是实际检案时用免疫组化方法检测吗啡的理想检材。     

甲维盐中毒死亡小鼠体内的分布及死后再分布

目的研究甲氨基阿维菌素苯甲酸盐(简称甲维盐)中毒死亡小鼠的致死血浓度、靶器官组织、毒物蓄积库和死后毒物再分布的特征。方法采用灌胃法建立中毒小鼠模型,动态观察急性中毒组、亚急性中毒组小鼠的主要中毒症状和临床死亡时间。观察中毒死后小鼠各器官组织病理形态学改变,应用酶联免疫吸附试验测定死后0、24、48、72h甲维盐体内分布及死后再分布,采用高效液相色谱法测定中毒小鼠的致死血浓度和死后各时间点的血中甲维盐浓度。结果中毒小鼠均在灌胃后15~30 min内依次出现神经、呼吸系统症状。急性中毒组小鼠的临床死亡时间为(45.8±7.9)min,亚急性中毒组为(8.0±1.4)d。甲维盐的急性致死血浓度范围为447.164 0~524.463 5 mg/L。光镜及荧光显微镜下各器官组织均见明显的病理改变;小鼠中毒死后72 h内,血、心、肝、脾、肺、肾及脑甲维盐浓度变化具有规律性(P0.05)。结论甲维盐中毒作用的主要靶器官为心、肝、肾、肺、脑和接触部位(胃),其主要蓄积库为肾、肝,甲维盐在小鼠体内存在死后再分布现象。     

大鼠死后心、肝、肾巯基含量的时序性变化研究

目的 测定大鼠死后不同时间心、肝、肾3种组织内总巯基(TSH)、非蛋白质巯基(NPSH)、蛋白质巯基(PSH)含量并探究其与死亡时间(Postmortem Interval,PMI)的关系。方法 健康大鼠颈部脱臼处死后，20℃恒温保存，分别于死后0 h、24 h、48 h、72 h、96 h、120 h、144 h、168 h提取大鼠心、肝、肾。利用吸光光度法，测定大鼠死后不同PMI 3种组织内不同类型巯基含量，分别建立其与PMI的相关回归方程。结果 大鼠死后168 h内，3种组织NPSH含量变化规律均不明显；心脏TSH与PSH含量随PMI无明显变化规律，而肝和肾TSH与PSH含量在24 h内升高，随后持续下降。肝、肾TSH和PSH含量与PMI的关系用二次方程拟合较好，其中肝TSH的相关系数最高(R²=0.834)，肾TSH和PSH以及肝PSH的相关系数较低(R²=0.768～0.825)。肝、肾TSH和PSH含量与PMI多元线性拟合关系较好(R²=0.862)。结论 肝组织内TSH含量与PMI相关性较好，可用于PMI推...     

溴敌隆及其代谢物-苄叉丙酮在犬体内的死后分布

目的研究溴敌隆及其代谢物-苄叉丙酮在中毒致死犬体内死后分布规律,为溴敌隆中毒检材的采取提供实验依据。方法分别经口给予犬2倍和4倍LD_(50)溴敌隆,待其死亡后迅速解剖取材,气相色谱-质谱联用法测定心血、外周血、尿、胆汁、心、肝、脾、肺、肾、脑、左下肢肌、膀胱、胃、胃内容、胰等脏器和体液中溴敌隆和代谢物-苄叉丙酮的含量。结果犬经2倍和4倍LD_(50)溴敌隆灌胃染毒后3d开始出现出血症状,(178.40±20.94)h后死亡。溴敌隆和代谢物-苄叉丙酮在各组织脏器及体液中的死后分布为:溴敌隆2LD_(50)组溴敌隆:胆汁尿、肝、心、肾心血、外周血、脾、肺等;苄叉丙酮:胆汁、尿、心血、外周血、肺、胃内容中含量高于其他脏器。溴敌隆4LD_(50)组溴敌隆:胆汁、尿肝、外周血心血、胃内容物等脏器。苄叉丙酮:胆汁、尿、肺浓度高于其他脏器。结论溴敌隆及其代谢物-苄叉丙酮在中毒致死犬体内死后分布不均匀,溴敌隆在胆汁、尿、肝脏、心血和外周血含量较高,代谢物-苄叉丙酮在胆汁、尿、肺较高。胆汁、尿、肝脏、心血、外周血可作为疑似溴敌隆中毒毒物分析的检材。     

组织细胞DNA含量变化与死亡时间的相关性研究

目的研究人死后各器官组织细胞DNA降解变化规律,探讨其在推断死亡时间方面的应用价值,为推断死亡时间提供科学依据。方法已知死亡时间人尸体的心、肝、脾、肾,按死后6,12,24和48h四个时间段取材,制成石蜡切片,经Feulgen染色并图像分析;同时将各器官组织按不同时间段取材,制成单细胞悬液,应用流式细胞仪检测DNA含量。结果(1)人体各器官组织细胞经FCM检测,脾细胞核DNA随死亡时间延长呈现较好的下降梯度,而心、肝、肾,则由于自溶较快,死后6h细胞核DNA含量已很低,其变化情况与死亡时间的相关性不佳;(2)各器官组织细胞核DNA染色强度指数均随死亡时间的延长而下降。结论(1)机体死亡后,各器官组织细胞核DNA含量随死亡时间延长逐渐减少,具有一定的变化规律,其中以脾细胞核DNA含量的变化趋势与死亡时间最具相关性,肝、肾次之,而心最差;(2)方法学分析,图像分析技术(IAT)与流式细胞术(FCM)两种检测方法在研究组织细胞DNA含量变化方面,各有利弊,可互补不足。     

大鼠电流损伤多器官c-Fos表达研究

目的探讨c-fos蛋白能否用于生前电击与死后电击的鉴别。方法建立大鼠生前与死后电流损伤模型。生前电击组大鼠于电击后即刻和1,2,4,8h处死;死后电击组大鼠于死后即刻和15、30min及1h电击大鼠,检测所有实验大鼠心、肝、脾、肺、肾、骨骼肌、皮肤、脑等器官c-fos蛋白的表达情况,其结果经图像分析处理。结果生前电击各组大鼠心、肝、肺、肾、骨骼肌、脑c-fos蛋白呈强阳性表达,脾脏与皮肤呈阴性表达;而于死后电击各组大鼠中,仅死后即刻电击组大鼠心、肝、肺、肾、骨骼肌、脑c-fos蛋白呈很微弱的阳性表达,其余各组各器官均为阴性表达。结论检测各器官c-fos蛋白的表达情况,可以鉴别生前电击与死后电击。     

短柄乌头急性中毒——乌头碱在大鼠体内分布的研究

本文用高效液相色谱法检测了大白鼠短柄乌头急性中毒后(LD_(50)剂量灌胃),乌头碱在心、肝、肾、血、脑内的含量分布。结果表明;体内乌头碱含量甚微或检不出。30例大鼠LD_(50)剂量灌胃后,16例2h内中毒死亡。其肝、肾内的乌头碱检出率明显高于心、血、脑,且中毒表现明显。另14例于2h整处死,其肝、肾、血中检出较高。16例2h内死亡组肝中乌头碱含量分析提示乌头碱在体内代谢很快。此结果为法医工作中乌头碱中毒案件调查、检材提取、毒物分析结果的评价提供了一定的依据。     

芬太尼中毒死亡大白兔体内分布研究

目的建立芬太尼中毒致死的动物模型,探讨芬太尼在致死大白兔体内的分布规律。方法用6只雄性大白兔按5.4mg/kg(2LD50)经耳缘静脉推注芬太尼注射液,大白兔死后迅速解剖并提取心、肝、脾、肺、肾、脑、肌肉、睾丸、胃、心血、周围血、胆汁和尿液,用正己烷∶乙醇(20∶1)萃取,利用UPLC-MSn法检测各组织和体液中芬太尼含量,使用SPSS15.0进行方差分析,均数两两比较的SNK法进行统计分析。检验水准为α=0.05。结果实验大白兔给药后1min出现颈项强直、四肢抽搐等中毒症状,平均4.7min因呼吸抑制而死亡。死后肺内芬太尼含量最高,其次是肾和心,而尿液中含量较低。结论本实验的结果与相关案例报道基本吻合,提示肺、肾和心脏是芬太尼中毒案件鉴定的理想检材,芬太尼在致死大白兔体内的分布规律可为相关案件的鉴定提供一定的依据。     

大鼠死后心血中吗啡浓度变化的HPLC检测

本文采用高效液相色谱（HPLC）分析技术检测了治疗量及中毒量吗啡肌注大鼠死后心血中吗啡浓度变化．结果表明．以治疗量吗啡肌注大鼠死后96h内，心血中吗啡浓度随死后时间增加而显著升高（P<0.01），吗啡浓度水平与死后时间呈显著正相关．以中毒量吗啡肌注大鼠死后12h内，心血中吗啡浓度无明显变化．死后24h、48h及96h．随死后时间延长，心血中吗啡浓度逐渐升高（P＞0.01），其递增强度不如治疗量吗啡组大鼠的明显．本研究证实死后尸体心血吗啡浓度明显受生前剂量的影响，且死后96h内，随死后时间延长心血中吗啡浓度不断增高．本文初步探讨了死后心血吗啡浓度变化发生的可能机制．为海洛因或吗啡中毒死亡的血液检测结果评判及死因分析提供理论依据．     

大鼠死后心血吗啡浓度变化的HPLC检测

采用高效液相邑谱分析技术（HPLC）检测治疗量及中毒量吗啡肌注大鼠死后心血中吗啡浓度变化。结果表明，以治疗量吗啡肌往大鼠，在死后96h内，心血中吗啡浓度随死后时间增加而显著升高（P＜0．01），吗啡浓度水平与死后时间里显著正相关；以中毒量吗啡肌注大鼠，在死后12h内，心血吗啡浓度无明显变化；死后24h、48h及96h，随死后时间延长，心血中吗啡浓度逐渐升高（P＞0．01），其递增强度不如治疗量吗啡组大鼠的明显.本研究证实，死后尸体心血吗啡浓度明显受生前剂量的影响，且在死后96h内，随死后时间增加．心血中吗啡浓度少数不断增高。     

The influence of site of collection on postmortem morphine concentrations in heroin overdose victims

When assaying for postmortem morphine concentration, significant site sampling variability exists between central and peripheral sampling sites and even within sampling regions of the body. To study the variation, 76 suspected heroin overdoses were identified. Each had femoral artery (FA) and vein (FV), left and right ventricle and pooled heart blood samples obtained at autopsy. Forty-four tested positive for morphine. Morphine concentrations were determined by gas chromatography/mass spectrometry, with sampling site differences reported as log-transformed ratios and compared by signed rank test.The mean FA to FV ratio for total morphine was 1.2 (range 0-4.5). The ratio for left heart to right heart total morphine was 1.1 (range 0.4-3.2). Left ventricular to FV total morphine ratio was 2.0 (range 0.6-6.9). In these opioid overdose deaths, FA and FV morphine concentrations are usually similar, although up to 4.5-fold differences were noted. Centrally obtained morphine concentrations are on average twice as high compared with peripheral morphine concentrations. Left and right ventricular morphine concentrations were usually similar, although up to 3.2-fold differences were noted (left side higher).     

Postmortem disposition of morphine in rats

The antemortem and postmortem distribution of morphine was studied in rats for the purpose of establishing whether drug distribution is altered after death. Samples were examined for free and total morphine concentration, pH and water content at 0-96 h after death. Morphine was administered antemortem at various intervals. All groups of rats studied showed a significant (P less than 0.05) increase in postmortem cardiac blood morphine concentrations. These changes, which are detectable within 5 min after death are likely to be related to an observed, rapid decrease in cardiac blood pH from 7.34 +/- 0.02 to 6.74 +/- 0.05. Significant increases in free morphine levels were, also, observed 24 and 96 h after death in liver, heart and forebrain while urine morphine levels decreased. The liver showed the greatest increase (20-fold) in free morphine levels 96 h after death, while hindbrain levels did not significantly change. Bacterial hydrolysis of morphine glucuronides accounted only in part for the observed increase in free morphine concentration. Postmortem fluid movement and pH-dependent drug partitioning was detected. It would appear that several mechanisms are responsible for postmortem drug distribution. Understanding the mechanisms and patterns responsible may eventually lead to better choices of postmortem tissue which may better represent antemortem drug levels.     

Distribution of morphine and morphine glucuronides in body tissue and fluids--postmortem findings in brief survival

An intoxication following administration of morphine, tramadol and atracurium in a suicide case is reported. The route of administration and the amount of the particular drug were known from the investigation of the death scene and the findings of the postmortem examination. Tramadol was present in the gastric contents as well as in blood, liver, kidney and brain samples, whereas the drug could not be detected in muscle. All body fluids and tissues investigated contained morphine as well as its 3- and 6-glucuronides with the exception of muscle tissue. The concentrations of morphine and its glucuronide metabolites were determined by LC/MS following solid phase extraction. Interestingly, the concentration of M6G in brain, liver and kidney were close to the concentration of M3G in the particular tissue. This phenomenon might be explained by a preferential hydrolysis of M3G or by a preferential formation of M6G postmortem. Measurement of morphine and M6G in femoral blood and cerebrospinal fluid may be a useful indicator in rapid deaths.     

大鼠百草枯中毒后体内的分布研究

目的建立生物检材中百草枯的超高效液相色谱-质谱联用检测方法,研究百草枯灌胃染毒致死的大鼠动物模型。方法大鼠以1/2 LD_(50)剂量灌胃染毒,分别于染毒后0.5h、2h、4h、8h、12h、24h、48h、72h处死解剖,采集心、肝、脾、肺、肾、脑、肌肉、膀胱和胃组织,UPLC-MS/MS法定量检测各组织中百草枯。结果试验中大鼠灌胃后,4h以内胃是主要分布器官,胃中含量最多,其他器官中含量相对较低。4h内除胃以外的脏器含量变化不大,4h后胃内百草枯含量有所下降,除胃以外的脏器含量均升高。各组织与脑组织比较具有显著性差异(P0.05)。结论百草枯在大鼠体内死后分布不均匀并且各组织含量随着时间变化有所改变。百草枯UPLC-MS/MS方法、口服染毒致死的动物模型、各组织分布规律可为甲百草枯中毒死亡案件提供检测依据。     

吗啡及其代谢物在藏毒致死者体内分布初探

目的采用固相萃取、液相色谱一串联质谱（LC-MS／MS）检验方法,考察吗啡和葡萄糖醛酸吗啡（M3G）在一例体内藏毒致急性死亡者体内分布情况。方法提取死者心血、尿、胃内容物、肝、肾、脑等15种检材,经Waters HLB小柱固相萃取后,C18色谱柱分离,采用电喷雾电离（ESI）、多反应监测模式（MRM）检测目标化合物。结果所建方法在0．0l～101μg／mL浓度范围内线性关系良好,提取回收率大于75％。结果显示总吗啡含量（游离态＋结合态）在胃内容物中最高,其次是尿、‘肾,在心血、胃组织、肺和腺体中居中,脑组织和心脏含量最低。结论本例检验结果验证了胃内容物、尿液和肾脏等是该类中毒案件的理想检材,其分布规律也可作为体内毒品分析实验依据。     

Tissue disposition of cocaine in man: a report of five fatal poisonings

The disposition of cocaine in five cases of fatal poisoning are presented. The highest concentrations of cocaine were found in urine, kidney, spleen, brain, lung and skeletal muscle. Cocaine concentrations in these organs far exceeded those in blood. Cocaine was detected in all other specimens tested including: bile, heart, liver, vitreous and adipose tissue. These results are in agreement with limited, previously reported, tissue data, and indicate that when urine is not available, kidney, spleen, brain and/or lung should be the specimen of choice for cocaine detection.