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素有“毒剂之王”之称的芥子气(HD)是目前危害最大的化学战剂之一,染毒后在体内可产生不同类型的特征性生物标志物,其对中毒诊断、溯源性分析以及毒理机制等研究有着重要的意义.本文首先采用同位素稀释-NCI-GC/MS分析方法监测和鉴定了HD体外全血染毒后产生的血红蛋白N端缬氨酸加合物(HETE-Val);其次,研究了不同剂量HD(0.02～0.15LD50)经皮染毒家兔体内HETE-Val的时效、量效关系.结果表明,HETE-Val与家兔中毒剂量间有良好的量效关系,而时效关系表明染毒后15min内即可产生并检测到HETE-Val,一周内达到最大,随后逐渐下降,但至染毒后第103天仍可监测到该加合物.与血红蛋白N端缬氨酸加合反应的HD仅占HD染毒总量的～0.15‰,与家兔血液反应的HD约占HD染毒总量的～1%.表明HETE-Val是一种重要的生物标志物,并可应用于HD暴露的确证和化学武器核查的溯源性检测.
Known as the “King of Toxic Agents”, mustard gas (HD) is one of the most harmful chemical warfare agents at present. After being poisoned, different types of characteristic biomarkers can be produced in the body. Its diagnostic value for poisoning, traceability Analysis and toxicological mechanism are of great significance.In this paper, isotope dilution-NCI-GC / MS was used to monitor and identify the hemoglobin N-terminal valine adduct (HETE- Val) .Secondly, the effect of dose-effect relationship of HETE-Val in rabbits transdermally exposed to different doses of HD (0.02-0.15LD50) was studied.The results showed that there was a good dose-effect While the time-effect relationship showed that HETE-Val was produced and detected within 15 min after exposure, reaching the maximum in one week and then decreasing gradually, but the adduct could still be detected at day 103 after exposure.Compared with hemoglobin N The HD of the valine addition reaction accounted for only ~ 0.15 ‰ of the total HD exposure and the HD response to rabbit blood was ~ 1% of the HD exposure, indicating that HETE-Val is an important organism Markers, and can be applied to the confirmation of HD exposure and chemical weapons verification of traceability testing.