Research On The Absorption And Transportation Of ZnO Nanoparteicles In Mice Small Intestine And The Effect On Intestinal Immunity

As new inorganic functional materials,zinc oxide nanoparticles?ZnO NPs?have good applications prospect in the fields of food industry,personal care products,and biomedical areas.However,studies showed that high dosage of ZnO NPs can accumulate in the body and induce toxic effects.Small intestines are not only the nutrient absorption place,but also the targeting organ of ZnO NPs.Studies on the absorption characteristics of ZnO NPs in the small intestines and their effect on intestinal immune function was still scarce.For a better understanding of the biosafety of ZnO NPs,the absorption characteristics,the effects on mice growth,and intestinal mucosal function of ZnO NPs in the small intestine after low-dose ZnO NPs exposure were evaluated.The contents are described as follows:In the first chapter,the application in food fields and solubility characteristics of ZnO NPs,and the research progress of the studies on their toxic effects on intestinal cells were reviewed.In the second chapter,the distribution of ZnO NPs in mice and its effect on their growth were investigated.By record the body weights change,we found that ZnO NPs promoted body weight increase significantly,with a better promotion of medium dose?62.5 mg/kg?than that of the high dose?125 mg/kg?and low dose?31.75 mg/kg?.By analyzing the zinc content in tissues and organs,we found that the zinc contents in vivo did not show significant changes compared with the control 24 h after the single intragastric administration.However,the zinc contents in liver,spleen,and kidney were significant higher after continuous administration of 28 d in 125 mg/kg dosage group.The results indicated that low doses of ZnO NPs can promote the growth of mice,and the zinc contents in vivo can still increase by long-term repeated exposure to low dosage of ZnO NPs.In the third chapter,the absorption characteristics of ZnO NPs were further studied in the small intestine.By analyzing the solubility of ZnO NPs in simulated gastric juice,the zinc contents in duodenum and ileum,the transcriptional level of genes related to Zn²⁺transport,the results showed that a large amount of ZnO NPs and ZnO dissolved in simulated gastric juice with pH 1.42 and 1.61,and the solubility decreases with the higher pH of simulated gastric juice.In addition,zinc content in duodenum and jejunum of ZnO NPs groups was significantly higher than that in jejunum and control group.The transcriptional level of Zn²⁺transport-related genes in jejunum was higher than that in jejunum and duodenum,and the gene expression related to zinc absorption and homeostasis in jejunum were higher than that of duodenum and ileum,and the gene expression in the bulk ZnO treatment group was higher than that ZnO NPs treatment group.The results demonstrated that ZnO NPs were mainly absorbed in the duodenum and jejunum,and can be absorbed mainly in the form of particles,compared with bulk ZnO.In the fourth chapter,the effects of ZnO NPs on the intestinal immune function in mice were mainly investigated.We investigated the gene expression of sIgA in small intestine and content of sIgA in intestinal juice,the contents of anti-inflammatory and pro-inflammatory cytokines in the small intestine and the expression of antioxidant-related genes in small intestine.We found that ZnO NPs can cause increase of gene expression of sIgA in intestinal tissue,and increase the secretion of sIgA.In addition,the contents of IL1?,IFN-?,and IL10 in small intestine increased,but the expression of IL6 was inhibited.Furthermore,the gene expression of antioxidant?SOD1,SOD2,CAT,HO-1?were upregulated with the low dosage of ZnO NPs treatment.These results showed that low dosage of ZnO NPs enhanced the humoral immunity of the gut,antioxidant and inflammatory response.