Protective effects of phloretin on immune hepatitis and its mechanism in mice
Objective To investigate the protective effects and regulatory mechanism of phloretin(PHL)on autoim-mune hepatitis(AIH)in mice.Methods 32 SPF Balb/C mice were randomly divided into normal control group,concanaval-in A(ConA)model group,PHL low-dose group and PHL high-dose group.The serum and liver tissues were extracted from the mice after 24 hours of modeling treatment.ELISA method was used to detect serum transaminases and inflammatory fac-tors;HE staining was used to observe pathological changes in liver tissue;TUNEL staining was used to detect liver cell apopto-sis;qRT-PCR was used to detect transcription expression level;immunohistochemistry and Western blot were used to detect the expression levels of inflammatory factors,autophagy and apoptosis proteins,and TRAF6-JNK pathway signaling proteins in liv-er tissue.Results Compared with the normal control group,the expressions of serum aminotransferase and inflammatory factors in AIH mice increased significantly(P＜0.001),and the pathological findings showed extensive destruction of liver tissue struc-ture,large-scale necrosis of liver cells and inflammatory cell infiltration.Compared with the ConA group,the levels of serum transaminase and inflammatory factors in the PHL group decreased(P＜0.05),the structure of hepatocytes was intact,and the necrotic area of hepatocytes was smaller(P＜0.05).In addition,compared with the ConA group,PHL significantly down-regu-lated the expression of pro-apoptotic protein and autophagy protein in liver tissue(P＜0.05),and down-regulated the activation of TRAF6-JNK signaling pathway(P＜0.05).Conclusion PHL may exert a protective effect on AIH mice by reducing liver cell autophagy and apoptosis,alleviating high inflammatory load.It may act through the TRAF6-JNK signaling pathway.
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