Inhibitory effect of metformin on inflammatory response of Kupffer cells of liver in diabetic mice and its improvement on phagocytic function / 吉林大学学报(医学版)

ABSTRACT

Objective:To observe the inhibitory effect of metformin on the inflammatory response of Kupffer cells (KCs) of liver in the diabetic mice, and to explore its improvement on the phagocytic function of KCs, and to elucidate the protective mechanism of metformin on the KCs in the diabetic mice.Methods:The C57BLKS/J db/db mice were divided into diabetes group and diabetes+metformin group, and the C57BLKS/J db/m mice were divided into non-diabetes group and non-diabetes+metformin group, 8mice in each group.The KCs were cultured in vitro and the changes of ultrastrustures of KCs were observed by transmission electron microscope.The levels of interleukin 6 (IL-6) , tumor necrosis factorα (TNF-α) andγ-interferon (INF-γ) in the KCs were detected by ELISA.The expression levels of intercellular adhesion molecule 1 (ICAM-1) protein in the KCs was detected by Western blotting method.Transwell chamber assay was used to detect the neutrophil chemotaxis ability of the KCs, and the phagocytic ability of KCs was observed under inverted microscope.Results:The number of mitochondria and rough endoplasmic reticulum (RER) in the KCs of the diabetic mice was reduced, the RER expanded, the mitochondria swelled, and the lipid droplets were increased.Compared with non-diabetes group, the levels of IL-6, TNF-α, INF-γand the expression level of ICAM-1in the KCs of the mice in diabetes group were significantly increased (P＜0.05) ;the neutrophil chemotaxis ability of the KCs was enhanced (P＜0.05) , and the phagocytic ability was decreased (P＜0.05) .Compared with diabetes group, the levels of IL-6, TNF-α, INF-γand the expression level of ICAM-1in the KCs in diabetes+metformin group were significantly decreased (P＜0.05) ;the neutrophil chemotaxis ability was decreased (P＜0.05) , and the phagocytic ability was enhanced (P＜0.05) .Conclusion:Metformin can inhibit the inflammatory response of KCs in the diabetic mice and improve its phagocytic function and protect the KCs.