| In recent years,the incidence of food allergies has risen sharply and has become one of the major public health issues.Generally,Ig E-mediated food allergic reactions occur rapidly,severely affecting consumers’ quality of life and economic burden.Studies have shown that interactions between microbial composition,metabolically active substances and dietary factors play a key role in food allergic reactions.Among them,amino acids,as the basic nutrients of human metabolism,are closely related to the histogenesis and organ development of the immune system.Among them,leucine(Leucine,Leu)and arginine(Arginine,Arg)serve as mammalian rapamycin target proteins.The upstream influence factor(Mammalian target of Rapamycin,m TOR)has been shown to be abnormal in the amino acid metabolism of sensitized mice,but related mechanisms have not been reported.Therefore,taking Leu and Arg as objects,to explore the changes of related pathways mediated by amino acid receptors and the mechanism of food allergic reactions,in order to explore the key points of clinical medicine for food allergies,and provide new food susceptible people.Diagnostic basis.The main research contents and results are as follows:(1)The combined Leu and Arg intervention and Leu alone intervention in Balb/c mouse oral gavage tropomyosin(TM)sensitization model significantly enhanced allergy indicators of TM sensitized mice,including Weight,allergic symptom score,temperature change during challenge,and serum levels of TM-specific Ig E,Ig G1,and Ig G2 a antibodies,etc.,but Arg alone had no significant effect on intervention;m TOR pathway inhibitor Rapamycin intervention can significantly improve the above allergies Sex indicators.Therefore,this study found that Leu and Arg play an important negative regulatory role in food allergies,and Rapamycin inhibits the m TOR signaling pathway to alleviate food allergic reactions caused by Leu and Arg intervention;(2)Both Leu and Arg can significantly increase the expression of MHCII and CD103 on the surface of DC cells and the relative expression of IL-6 and IL-12 genes.At the same time,the corresponding indicators of Rapamycin have decreased;Leu and Arg combined intervention passed Enhance the differentiation of IL-4 + Th2 cells in spleen cells of sensitized mice to inhibit the differentiation of IFN-γ + Th1 cells and promote allergic reactions in mice;Arg intervention significantly enhanced the differentiation of IL-17 A + Th17 cells and promoted the occurrence of inflammatory reactions;(3)Leu and Arg intervention activated its amino acid receptors Sesn2 and SLC38A9 and Cyclin D1 and S6 K genes downstream of the m TOR signaling pathway;Leu and Arg combined intervention and Leu alone intervention could activate the NF-κB signaling pathway to a certain extent,while Rapamycin The effect of the intervention disappeared,indicating that after the activation of the m TOR signaling pathway by Leu,a stream of information may occur with the NF-κB signaling pathway;(4)Bone marrow-derived DC cells were induced and cultured in vitro for phenotypic identification.Leu and Arg and m TOR and NF-κB inhibitors were used as interventions to conduct experiments.The results show that Leu and Arg interventions can promote the differentiation of DC cells and promote m TOR.Phosphorylation and IκBα protein expression,further studies found that Leu interfered with activation of the m TOR / NF-κB signaling pathway and promoted DC cell-mediated Th2 differentiation to inhibit Th1 cells;and Arg promoted cytokines of Th17 cells by activating the NF-κB signaling pathway And the expression of transcription factors thus play a negative role in regulating food allergies. |