Jichu yixue yu linchuang (Jan 2024)
Wogonin promotes Th17/Treg cell balance in rat models with autoimmune hepatitis
Abstract
Objective To investigate the impacts of wogonin (WG) on Th17/Treg cell balance in autoimmune hepatitis (AIH) rats. Methods A total of 10 rats were randomly selected as the control group. The remaining rats were injected with concanavalin A (ConA, 12.5 mg/kg) solution via tail vein to construct AIH model rat, which were randomly divided into AIH group, L-WG group (10 mg/kg), M-WG group (20 mg/kg), H-WG group (30 mg/kg), H-WG+VPA group (30 mg/kg WG+300 mg/kg Notch signal pathway activator VPA), 10 rats in each group and administered once a day for 10 days. Serum inflammatory factors and liver function indexes were detected by ELISA; HE staining was used to observe the pathological morphology of liver tissue; the level of spleen Th17/Treg cells was detected by flow cytometry; Western blot was used to detect the expression of spleen retinoid acid related orphan receptor γ t (RORγt), fork head box protein P3 (Foxp3) and liver Notch signal pathway proteins. Results The liver tissue structure of control group was normal and the staining was clear; In AIH group, the cells of liver tissue showed edema, the increase of cell volume led to the compression and narrowing of liver sinuses, and a large number of inflammatory cell infiltration and a small amount of necrosis occurred. The contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-17 and IL-23, level of Th17 cells, Th17/Treg, the expression of RORγt, Notch, hes family bHLH transcription factor 1 gene (HES1) and hes related family bHLH transcription factor with YRPW motif 1 (HEY1) protein in AIH group were greatly higher than those in control group (P＜0.05), the contents of IL-10 and TNF-β, level of Treg cells, and level of Foxp3 protein were greatly lower(P＜0.05); Compared with AIH group, the liver injury in L-WG group, M-WG group and H-WG group was improved, the contents of ALT, AST, IL-17 and IL-23, level of Th17 cells, Th17/Treg, the expression of RORγt, Notch, HES1 and HEY1 protein were greatly lower (P＜0.05), the contents of IL-10 and TNF-β, level of Treg cells, and level of Foxp3 protein were greatly higher (P＜0.05); VPA reversed the improvement effect of H-WG on AIH rats. Conclusions WG could promote Th17/Treg cell balance in AIH rats by down-regulating Notch signal pathway.
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