摘要
目的研究乙醇对地西泮半数致死量及早期代谢的影响。方法 1利用AOT425tat Pgm程序测定雌性小鼠经口灌服地西泮单独或与不同剂量乙醇联合染毒时的半数致死量;2低、中、高剂量(50、100、200mg/kg)地西泮单独或与不同剂量乙醇联合染毒,HPLC法测定染毒后15、30、60min时小鼠心血中地西泮及其主要代谢物去甲西泮、奥沙西泮血药浓度,观察染毒早期乙醇对地西泮代谢的影响。结果 1联合染毒使地西泮LD50值明显降低,且下降幅度随乙醇剂量增加而加剧;2各联合染毒组染毒15、30、60min时地西泮、奥沙西泮血药浓度较单独染毒时低;50、100mg/kg地西泮与乙醇联合染毒60min时去甲西泮浓度较单独染毒显著升高,但乙醇剂量影响不大;高剂量地西泮与低、中剂量乙醇联合染毒60min时去甲西泮浓度较单独染毒组时低。结论 1地西泮与乙醇确有毒性协同作用,联合中毒时地西泮半数致死量变化与乙醇剂量有关;2染毒早期,乙醇可使地西泮及奥沙西泮血药浓度降低,同时抑制去甲西泮的代谢,使其药浓度升高,在毒性协同效应发生中有意义。
Objective To investigate the influences of ethanol on the median lethal dose and metabolism of diazepam（DZ）. Methods ①The acute oral toxicity experimental AOT425 program was used to determine the median lethal doses （ LD_50 ） of diazepam when used alone and combined with different doses （ low, medium and high dose） of ethanol to female mice. ②Female mice were exposed to different doses of DZ （50mg/kg, 100mg/kg, 200mg/kg） alone and combined with different doses of ethanol respectively. HPLC was implied to detect the concentrations of DZ and its main metabolites, nordiazepam （NDZ） and oxazepam（ OXZ）, in heart blood at early stages（ 15min, 30min and 60min）. Results ①The LD_50 values of diazepam were lower in DZ ＋ Ethanol groups. The decrease of LDs0 value was positively correlated with the increase of ethanol dosage.②In the DZ ＋ Ethanol groups, the concentrations of DZ and OXZ were lower than DZ groups in the early stages, in 50mg/kg, 100mg/kg DZ ＋ Ethanol groups,the concentrations of NDZ were significantly higher at 60min than 50mg/kg, 100mg/kg DZ groups, but the effect of ethanol dosage was not obvious; in 200mg/kg DZ ＋ Ethanol （low, medium dose） groups, the concentrations of NDZ were lower than the 200mg/kg DZ group at 60min.Conclusion ①There was toxicity synergy （ interaction ）between diazepam and ethanol. diazepam changes with ethanol poisoning. ② Nordiazepam may early stage of toxicity synergy The LD_50 value of dosage in combined be meaningful in the （ toxic interaction ） between diazepam and ethanol.
出处
《中国法医学杂志》
CSCD
2015年第1期5-8,共4页
Chinese Journal of Forensic Medicine
基金
国家自然科学基金青年基金项目(81102299)
中央高校基本科研业务费项目(HUST:2013TS113)
教育部博士点新教师基金项目(20110142120034)
关键词
法医毒理学
地西泮
乙醇
半数致死量
协同效应
forensic toxicology
diazepam
ethanol
median lethal dose
synergistic effect
