金属化学形态纳米识别- FI-HPLC/GC-ICP-MS联用分析及代谢组学研究

The migration and transformation of metal or metals chemical species in the environment could cause serious public health problem. But there was still lack of effective method for chemical exposure recognition and detection of metal species in health analysis, and the toxicity mechanism of metal chemical species to health was unclear. A serials new nanomaterials (NMs) and molecularly imprinted polymer which matching six kinds of metal species would be synthesized according to their chemical characteristics, and employed to explore efficient selective recognition of indicator metal species, imprinting principle, adsorption law and dissolution methodologies. The model of reactive mechanism between NMs and related metal species was proposed to build up. A flow chart programme of speciation of off-line to on-line (O2O) for chemical identification and detection of metals species was planned to set up based on self-assembled NMs coupled FI-HPLC/GC-ICP-MS/AFS/GFAAS hyphenated technology. The metabolic effect and poison mechanisms of different metals species exposed to living environment was studied based on metabonomics method through animal test coupled NMs-uHPLC-ESI-MS-MS hyphenated instrument. Metabolic pathways of metals species were discussed and metabolic biomarkers were obtained to serve for new biometric monitoring method. These results would provide new theoretical and technical data for heavy metals toxic analysis, food safety and environmental/occupational health.

金属或类金属化学形态在环境中迁移转化可能引发严重的公共卫生问题，但卫生分析中金属元素化学形态的暴露识别和检测尚缺少有效方法，金属形态对健康的作用机制还不清楚。本研究针对六种指标金属的化学形态特性，匹配性合成新型纳米材料和印迹聚合物，探讨典型金属化学形态的高效选择性识别、印迹原理、吸附规律和溶出方法；构建纳米材料与金属化学形态相互作用机制模型；基于纳料材料自组装（NMs）-FI-HPLC/GC-ICP-MS/AFS/GFAAS联用技术，建立金属形态O2O化学识别和检测流程；基于代谢组学方法和NMs-uHPLC-ESI-MS-MS联用分析，研究环境暴露不同形态金属所致生物效应、代谢机制和毒作用本质。构建金属化学形态代谢指纹图谱，探明金属形态体内分布及作用规律。解析金属形态的代谢通路，发现其环境暴露代谢标志物及生物识别监测新方法。为金属毒物分析、食品安全、环境/职业卫生控制提供科学依据。

环境和食品中金属或类金属毒性与其存在的化学形态有关，但卫生分析中金属元素化学形态暴露识别和检测尚缺少有效方法，不同金属形态对健康的影响机制还有待阐明。针对汞、锡、铜、镉、铬等多种金属元素，本研究合成、筛选了氨基修饰磁性氧化石墨烯、不同结构的二硫化钼、氮化碳及异质结等纳米材料并进行了化学和生物学表征；探讨了金属化学形态与纳米材料相互作用规律，构建了基于纳米材料的色谱（HPLC/GC）-光谱及质谱（AFS/ICP-MS）联用分析方法；利用uHPLC-ESI-MS-MS和GC-TOF-MS代谢组学技术开展了金属化学形态（特别是汞、锡等蓄积性金属有机形态）代谢通路和代谢标志物分析。结果表明，高磁性氧化石墨烯材料植入氨基基团能大大提升对镉和铜离子的吸附性和选择性；合成的六方相二硫化钼（MoS2）纳米材料片层间距为0.69-0.83nm，基体和纳米片之间的阶跃高度约5.8nm，具有较大的内层空间，对汞离子、甲基汞和乙基汞都具有高效吸附和解吸能力，与HPLC联用分离后可实现AFS和ICP-MS检测；合成的金属相二硫化钼（1T-MoS2)修饰GCE电极LOD为1.54×10-19mol/L，比2H-MoS2修饰GCE电极LOD值1.46×10-13mol/L低六个数量级；有机化学形态与离子态汞毒性差异机制可能与破坏血脑屏障的转运功能，导致L-多巴向脑部转运减少，脱羧形成多巴胺的过程被抑制有关；低剂量（10ng/mL）甲基汞暴露能显著降低实验动物肠道和大脑肌醇水平，肌醇及相关代谢通路在甲基汞毒性中发挥了重要作用；肠道菌群参与介导有机锡化学形态导致的实验动物脂质代谢紊乱和金属元素代谢异常，而金属元素代谢与人体疾病及感染有密切关系。本研究建立了用新型纳米材料检测金属化学形态新方法，并揭示了不同化学形态金属毒作用新机制，为金属毒物分析、环境/食品安全评价提供了科学依据。