低剂量白细胞介素-2对自身免疫性肝炎小鼠的肝保护作用及其机制
Protective effect and its mechanism of low-dose interleukin-2 against hepatocyte injury in mice with autoimmune hepatitis
摘要
Abstract
Objective To investigate the protective effect and its mechanism of low-dose interleukin-2(IL-2)against hepatocyte injury in Concanavalin A(Con A)-induced autoimmune hepatitis(AIH)mice.Methods Eighteen SPF female C57BL/6 mice were randomly divided into normal group,model group and treatment group,each group with 6 mice.Mice in the treatment group were subcutaneously injected with 300 μl 10,000 U IL-2 for 12 d,once a day.2 h after the last dose,Con A(15 mg/kg)was injected through the tail vein in the model group and treatment group.After 8 h of modeling,the histopathological changes in the mouse liver were observed using HE staining,and the serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),tumor necrosis factor-α(TNF-α),and interferon-γ(IFN-γ)were detected using ELISA method;the expression of apoptotic protein caspase 8/9/3 was detected by Western blotting;and the percentages of Treg and Th1 cells were observed by flow cytometry.Results Compared with normal group,the liver index,spleen index,the percentage of necrotic area of liver tissue,the serum levels of ALT,AST,TNF-α and IFN-γ,and the expression of apoptosis protein caspase 8/9/3 significantly increased in the model group(P<0.05 or P<0.01);Compared with model group,the liver index,spleen index,the percentage of necrotic area of liver tissue,the serum levels of ALT,TNF-α and IFN-γ,and the expression of apoptosis protein caspase 8/9/3 significantly decreased in the treatment group(P<0.05 or P<0.01).The flow cytometry results showed that compared with normal group,the percentages of Treg and Th1 cells and Th1/Treg ratio increased in the model group(P<0.05 or P<0.01);Compared with the model group,the percentage of Treg cells further increased(P<0.01),Th1/Treg ratio decreased significantly in the treatment group(P<0.05),but there was no significant difference in the percentage of Th1 cells between two groups(P>0.05).Conclusion Low-dose of IL-2 can effectively improve liver injury in AIH mice,and the mechanism of action may be related to inducible Treg cell activation.关键词
自身免疫性肝炎/白细胞介素-2/调节性T细胞/Th1细胞Key words
autoimmune hepatitis/interleukin-2/regulatory T cells/Th1 cells分类
临床医学引用本文复制引用
陈晨,李竹蓉,吕思学,郭地,武嘉文,杨娜,刘杨..低剂量白细胞介素-2对自身免疫性肝炎小鼠的肝保护作用及其机制[J].解放军医学杂志,2025,50(2):214-220,7.基金项目
This work was supported by the Shanxi Provincial Key Country Science and Technology Cooperation Project,Shanxi Provincial Science and Technology Department(202104041101013),the Key Team of Science and Technology Innovation Talents of Shanxi Province for Prevention and Treatment of Rheumatological and Immunological Diseases by Integrated Chinese and Western Medicine(202204051002033),the Science and Technology Innovation Team Project of Shanxi University of Traditional Chinese Medicine(2022TD2003),and the Discipline Construction Project of Shanxi University of Traditional Chinese Medicine(2023XKJS-03) 山西省科学技术厅山西省重点国别科技合作项目(202104041101013) （202104041101013）
中西医结合防治风湿免疫病山西省科技创新人才重点团队(202204051002033) （202204051002033）
山西中医药大学科技创新团队项目(2022TD2003) （2022TD2003）
山西中医药大学学科建设项目(2023XKJS-03) （2023XKJS-03）
