大米主食基质中污染物镉的肠吸收转运机制研究

For serious problem of rice cadmium (Cd) pollution and the potential health hazards of long-term and low dose exposure, it is extremely important to assess dietary exposure scientifically and to carry intervention-regulation. The prerequisite is to grasp the mechanism of intestinal absorption and transport of Cd in staple food matrix for contaminated rice. The established model system of Caco-2/HT29 cell co-culture is applied in the project to simulate intestinal absorption and transport, with supplemented by animal experiment. The effect of the multicomponent in staple food for rice on the absorption and transport of cadmium is to research using data mining technology, to clearly definite multiple factors of matrix, complex conditions, and laws. On this basis, it is to clarify the main Cd speciation and analyze its pathway during the intestinal absorption and transport process. Furtherly, it is to illuminate the intrinsic mechanisms of matrix effect-Cd amount-Cd speciation-Cd pathway during the absorption and transport. It is also to establish the passivation method in situ to prevent intestinal absorption and transport of cadmium in the staple food for rice matrix. This project will provide important evidence to improve the dietary exposure assessment of cadmium of contaminated rice and to accurately intervene and control.

面对严重的大米重金属镉污染及其长期低剂量暴露给人类健康带来的潜在危害，对其进行科学的膳食暴露评估及干预调控极为重要，但其先决条件是要掌握大米主食基质中镉的肠吸收转运机制。本项目采用申请人已建立的Caco-2/HT29细胞共培养的肠吸收转运模型，辅以动物实验验证，利用数据挖掘技术研究大米主食基质中多组分变化与镉的吸收转运关联性，明确影响镉的肠吸收转运的多种基质因素、复杂条件及规律，在此基础上，表征镉的肠吸收转运形态特征，解析其吸收转运通路，从而阐明大米主食基质影响效应-镉吸收转运量-镉形态-镉转运通路四者间的内在关联机制，建立大米主食基质中镉的肠吸收转运的原位钝化方法，为完善大米中污染物镉的暴露评估及精准干预调控提供重要依据。

本项目深入阐明了大米主食基质中污染物镉的肠吸收转运机制，为完善其科学暴露评估及精准干预调控提供重要依据。首先，通过研究构建出更接近人体正常生理状态的有效模拟肠吸收的快速共培养Caco-2/HT-29（70:30）细胞模型，明确了蒸煮米饭中污染物镉的生物可给性和生物有效性，且发现EGCG能显著降低消化液中镉吸收转运。在此基础上，进行了SD雌性大鼠短期、生长期内糙米和精米两种米饭基质中镉暴露研究，首次运用药代动力学方法研究了镉与其它金属元素机体内吸收、排泄动力学行为差异，发现与其他金属元素相比，糙米中内源性组分膳食纤维（结合性多酚）等能明显减弱机体对镉的胃肠道吸收，并促进镉通过粪便排出体外。进一步发现，糙米米饭基质中内源性组分还能通过修复肠道屏障、增加肠道微生物丰度和多样性、保护肠道微生物群落稳态及促进镉肝肾排出等机制缓解镉毒性。此外，还揭示出米饭基质中镉长期低剂量暴露对生长期大鼠机体能产生明显的健康危害，主要表现在，盲肠处对镉的吸收显著增加，导致性激素水平失调、内分泌紊乱，肝脏、肾脏血清生化指标异常，部分实验大鼠肝脏、肾脏、肺部、十二指肠和盲肠出现明显病变；破坏肠道微生物群落稳态，使得Firmicutes、Lachnoclostridium丰度增加，Muribaculaceae、Roseburia丰度降低，指示宿主的能量代谢减弱，肥胖、动脉粥样硬化风险加大；镉能在雌性大鼠体内快速蓄积并破坏细胞膜运输，导致体内脂质代谢和氨基酸代谢过程中产生过多的促炎代谢物，影响大鼠的消化系统和内分泌系统。最后，建立了大米主食基质中镉的肠吸收转运原位钝化方法，利用EGCG、酵母等物质进行干预降低镉胃肠吸收，进而减轻其毒性及危害。本项目对揭示食品基质中真实性镉暴露危害及风险提供了新着眼点，为食源性镉暴露的食品基质干预剂开发提供了新思路，对保护公众健康特别是儿童具有重要现实指导意义。