Glycolysis Participates In Hashimoto's Thyroiditis By Regulating Macrophage Polarization

Objective: Hashimoto thyroiditis(HT)is one of the common diseases of the endocrine system.In this study,we investigated the changes in peripheral blood macrophage polarization and metabolic patterns in patients with HT,and explored the effects of metformin(Met)and 2-Deoxy-D-glucose(2DG)on the energy metabolism and polarization status of peripheral blood macrophages in order to provide information on the treatment targets and treatment strategies.Methods: Thirty patients and thirty healthy person(healthy control,HC)were randomly selected and lymphocyte separation fluid was used to extract mononuclear cells(PBMCs)from the peripheral blood of the all subjects.Flow cytometry was used to detect the ratio of M1 and M2 macrophages in PBMCs.Purified monocytes was obtained by Stemcell RosetteSep method and cultured by serum culture with 10 ng/ml GM-CSF in vitro and the cell culture supernatant was collected after seven days culture.The macrophages were separated and purified and the cell culture supernatant was collected.The levels of IL-10,IL-6 and TNF-? were detected by Immune enzyme-linked immunosorbent assay(ELISA).The glycolysis level of the sorted macrophages and the changes of it were detected by seahorse energy metabolism analyzer analyze the changes.The ratio of M1 and M2 macrophages and the level of glycolysis were measured after treating with Met and 2DG.Results: Compared with the HC group,the expression of surface molecules CD80 and CRR2 of M1 macrophages in HT patients was higher than that in the control group,and there was a statistical difference(P < 0.05).In addition,the inflammatory factors TNF-?and IL-6 secreted by M1 macrophages were significantly higher than those in the control group(P < 0.05).Also the glycolysis of macrophages in HT patients was increased significantly after activation compared with HC group(P < 0.05).After exposing to Met and 2DG,the glycolysis level of macrophages was decreased,and M1 macrophages were polarized toward M2(P < 0.05).Conclusions: Imbalance of macrophage M1/M2 polarization and abnormal immune metabolism of macrophages were found in the patient with HT.Met and 2DG can inhibitthe glycolytic metabolic pathway and improve the polarization of macrophages.Macrophages are involved in the occurrence and development of HT,and abnormal immune metabolism plays an important role in the mechanism of macrophage polarization imbalance.