乌头碱、新乌头碱、次乌头碱及其代谢物在中毒家兔体内的死后再分布研究

Postmortem Redistribution of Aconitine,Mesaconitine,Hypaconitine and Their Metabolites in Poisoned Rabbits

研究乌头碱、新乌头碱、次乌头碱及其代谢物(苯甲酰乌头原碱、苯甲酰新乌头原碱、苯甲酰次乌头原碱、乌头原碱、新乌头原碱和次乌头原碱)在中毒家兔体内的死后再分布规律,为乌头属中药中毒案件的检材选取提供依据。家兔18只,随机分成6组,采用灌胃方式建立乌头碱中毒家兔模型,2 h后气管夹闭处死,仰卧位置于25℃条件下保存,分别于死后0、4、8、12、24、48 h进行解剖取材,取心血、外周血、尿液、心脏、肝脏、脾脏、肺脏、肾脏,采用高效液相色谱-串联质谱法检测各生物检材中不同物质的含量。结果表明:尿液中苯甲酰新乌头原碱和苯甲酰次乌头原碱48 h的含量分别是0 h的2.39倍和2.51倍;心血和外周血中苯甲酰新乌头原碱含量呈上升趋势,且在外周血中含量远高于心血;各物质在脾脏、肝脏、肾脏中的含量明显高于心脏和肺脏,次乌头碱和苯甲酰次乌头原碱在三者的含量呈上升趋势,且在脾脏中最高,12 h后苯甲酰新乌头原碱在三者中均呈上升趋势。乌头碱、新乌头碱、次乌头碱及其代谢物在家兔体内存在死后再分布现象,尿液、脾脏、肝脏、肾脏可作为乌头属中药中毒的优选毒物分析检材。

Aconitum is of pharmacological effects,therewith making it be used to exert analgesic,antiepileptic and anti-inflammatory functions at clinic for years.However,aconitum is of high toxicity derived from diester-diterpenoid alkaloids(DDAs)including aconitine,mesaconitine and hypaconitine,usually leaving narrow therapeutic safety-window time.The lethal dose of aconitine is estimated to be only 1-4 mg for human adults so that homicidal and/or suicidal cases are often reported of involving with aconitum.The diester-diterpenoid alkaloids could change their structures and toxicities quickly during in vivo processing and metabolism,having become into monoester-diterpenoid alkaloids or further the alcohol amines.Thus,aconitum alkaloids deserve the in vivo research of their metabolites especially on the time when there haven’t been few studies on postmortem redistribution of aconitum alkaloids in poisoned animal.Consequently,the postmortem redistribution of aconitine,mesaconitine,hypaconitine and their metabolites(benzoylaconine,benzoylmesaconine,benzoylhypaconine,aconine,hypaconine,mesaconine)was here studied.The 18 experimental rabbits were randomly divided into six groups,being poisoned by intragastric administration.On 2 hours after administration,the rabbits were killed by trachea closing and kept in supine position at 25°C,waiting for collection of tested samples(heart blood,peripheral blood,urine,heart,liver,spleen,lung and kidney)at post-death of 0,4,8,12,24 and 48 h.The high performance liquid chromatography-tandem spectrometry was adopted to determine the collected samples,showng as urine:the benzoylmesaconine and benzoylhypaconine were respective 2.39 and 2.51 times higher of their contents at 48 h than at 0 h;heart blood and peripheral blood:benzoylmesaconine displayed an obvious upward trend,with its content being much higher in peripheral blood than in heart blood;viscera tissues:each substance was significantly higher of content in spleen,liver and kidney than in heart and lung,with hypaconitine and benzoylhypaconine showing overall content-upward trend in spleen,liver and kidney,even demonstrating highest of the two in spleen,plus the benzoylmesaconine at post-death 12 h showing an upward trend in spleen,liver and kidney.Accordingly,the postmortem redistribution of aconitine,mesaconitine,hypaconitine and their metabolites was revealed in rabbits poisoned,potential to provide reference for aconitum alkaloids poisoning cases to select samples and carry out relevant forensic identification.Evidently,urine is the most obvious biological sample for aconitum poisoning,and also harboring the highest content of each substance at the time of death,therefore prominent as the collecting sample in cases of suspected aconitum poisoning.Whereas,when the time of death is long and it is difficult to collect the liquid biological samples,the tissues of spleen,liver and kidney might be used as the canadidate biological samples in aconitum poisoning.