海洛因(Heroin)是迄今为止滥用最多、依赖潜力最强的吗啡衍生物。海洛因及代谢产物O6-单乙酰吗啡、吗啡、吗啡-3-葡萄糖苷酸和吗啡-6-葡萄糖苷酸在中枢神经系统(CNS)的作用浓度与其毒性和成瘾性密切相关，而血脑屏障中多药耐药相关蛋白2(MRP2)可以识别海洛因代谢产物并调控其在CNS的浓度。因为海洛因及代谢产物与血脑屏障上MRP2的相关性目前还没有研究进行系统阐述，所以本项目紧紧围绕血脑屏障MRP2与海洛因代谢组学相关性这一核心问题，从“体外-体内”、从“外排现象-转运机制”和从“单个样本-代谢组学”三个方面进行代谢组学研究。希望获得MRP2影响下海洛因及代谢物在血脑屏障中主动转运的明确证据，阐明在中枢神经系统中海洛因代谢组学的化学生物学机制，为法医毒物分析研究中海洛因的毒性和成瘾作用机制提供科学依据。

Heroin is most indiscriminately used and addictive morphine derivatives. It has a series of metabolites including 6-monoacetyl morphine, morphine, morphine-6-glucuronide and morphine-6-glucuronide. The transport process of heroin and its metabolites through blood brain-barrier(BBB) to central nervous system(CNS) has a close correlations with efflux proteins. Multidrug resistance-associated protein 2(MRP2) which located on brain capillary endothelial cell membrane could identify specific compounds and transport them through BBB. This effect could preserve a relative stable environment within CNS. As there is no systematic study upon the interactions between heroin metabolites and transporters on BBB, we intended to focus on this core issue of heroin metabolomics. Started with concentration-dependent effect of efflux proteins to heroin, we investigated the chemico-biological of heroin in CNS. Through systematic interpretation of heroin metabolomics in CNS, the definite evidence of correlations between heroin and its metabolites and MRP2 in BBB could be obtained. This project illustrated the molecular mechanism of heroin metabolomics in CNS, and it could provide reliable scientific evidence for heroin addiction and toxicity in forensic toxicological investigations.