氯化镧和柠檬酸镧在胃肠道以磷酸镧微粒为转化物种且主要通过M细胞进行转运吸收

摘要

本工作以氯化镧(LaCl3)和柠檬酸镧(LaCit)为代表性化合物,对稀土在消化道内的物种存在形式及吸收转运机制进行了研究和探讨.研究采用了人工胃液和肠液模拟体内消化道环境.电感耦合等离子体质谱(ICP-MS)检测结果表明,大于99.9％的La发生了沉淀.散射光粒度(DLS)分析结果显示,这些微粒的平均粒径由200 nm(孵育2 h)增大到600 nm左右(孵育24 h),这表明微粒之间发生了聚集.傅立叶变换红外光谱(FTIR)研究表明,稀土微粒的主要成分为稀土磷酸盐.为研究稀土在肠道中的吸收转运机制,以LaCit(2或100 mg/kg/day)对小鼠灌胃给药7天,取小肠的普通肠段和派氏结进行了ICP-MS分析.派氏结中的La含量明显高于普通肠段,这提示稀土微粒可能主要由派氏结上淋巴滤泡上皮中的M细胞吞噬转运.此外,建立了Caco-2细胞单培养模型和Caco-2/Raji B细胞共培养模型分别模拟小肠上皮和滤泡上皮.结果显示,Caco-2/Raji B细胞共培养模型转运的La含量显著高于Caco-2细胞单培养模型(大约60倍左右),且Caco-2细胞单层透过的镧的量极低,这说明M细胞是吸收转运磷酸镧的主要途径.以上结果表明氯化镧和柠檬酸镧在胃肠道主要以磷酸镧微粒形式通过M细胞进行转运吸收.本研究将为稀土在农业和医学中的合理应用提供科学依据.%In the present study,we investigated the transformed species and the absorptive mechanism of rare earth elements (REEs) in gastrointestinal (GI) tract,using LaCl3 and LaCit as representative compounds.Artificial gastric and intestinal fluids were used to simulate the environment of the digestive tract in vivo.The inductively coupled plasma mass spectrometry (ICP-MS) result showed that more than 99.9％ of LaCl3 and LaCit formed precipitation in artificial intestinal fluid,with the average size distribution of 200 nm (2-h incubation) increasing to 600 nm (24-h incubation) determined by dynamic light scattering (DLS),indicating the aggregation of the particles.The Fourier transform infrared spectroscopy (FTIR) analysis demonstrated that the constituents of these particles were mainly in the form of lanthanum phosphates.To explore the transport mechanism of REEs in GI tract,the mice Peyer's patches (PPs) and intestinal epithelium were separated to evaluate the content of lanthanum by ICP-MS following oral administration with 2 or 100 mg/kg/day of LaCit for 7 d.The results showed that the amount of lanthanum phosphate particles absorbed by PPs was significantly greater than that of intestinal epithelium,indicating that lanthanum particles might be phagocytosed mainly by M cells located in the follicle-associated epithelium (FAE) overlying PPs.Furthermore,Caco-2 cell monoculture and Caco-2/Raji B cell coculture models were established to simulate intestinal epithelial cells and FAE,respectively.The result showed that the transport of lanthanum in Caco-2/Raji B coculture model was significantly higher than that in Caco-2 monoculture model (about 60 times higher),and the level of lanthanum in the basal compartment of Caco-2 monoculture model was very low,supporting that M cells were the main route for lanthanum phosphate particles to be transported and absorbed.Taken together,these data suggested that LaCl3 and LaCit in GI tract were absorbed mainly via M cells with lanthanum phosphates as transformed species.The obtained results would provide the theoretical basis for the rational application of REEs in agriculture and medicine.