关键词: 原发性胆汁性肝硬化, 脾切除, 肝纤维化, 转化生长因子-β1, 小鼠

Abstract: Objective To investigate the effects of splenectomy on hepatic fibrosis in mice with poly I:C-induced primary biliary cholangitis（PBC）. Methods Forty C57BL/6 female mice were randomly divided into the splenectomy group （n=10）,sham-operation group （n=10）,model control group （n=10） and normal control group （n=10）. Mice in the first three groups were injected with poly I:C to establish PBC models,while animals in the control were injected with equal volume of saline. At the end 20 weeks,splenectomy was performed in ten mice, and sham operations were performed in another ten mice. Liver index,liver function index and liver histology were performed at each group at the end of 32w. The mRNA levels of TGF-β1,TβRI and TβRII in liver tissues were assayed by RT-PCR,and TNF-α levels in terminal ileum were detected by ELISA. Results At the end of 32 weeks,the liver index were （41.5±5.2）,（39.6±7.5）,（39.1±1.0） and （53.2±2.1）,in splenectomy,sham-operation,model and control group,respectively （P<0.05）;serum ALT,AST and ALP levels in splenectomy group were （43.5±6.4）U/L,（157.7±20.9） U/L and（178.1±38.0） U/L,significantly lower than those in model group[（52.0±9.0） U/L,（183.4±12.4） U/L and（195.3±62.6） U/L,P<0.05 for all];liver fibrosis staging in splenectomy group were significantly milder than those in sham-operation and model control group;hepatic TGF-β1,TβRI,TβRII mRNA levels were （0.5±0.09）,（0.5±0.05） and （0.5±0.09） in splenectomy group,significantly lower than those in model group [（1.0±0.10）,（1.0±0.08） and（1.0±0.09）,P<0.05];the TNF-α level in terminal ileum homogenate was （50.0±8.6）ng/L in splenectomy group,obviously lower than[（106.8±19.8） ng/L,P<0.05] in model group. Conclusion Splenectomy could relieve the progression of liver fibrosis in PBC mice,which might be related to the inhibition of hepatic TGF-β1 and ileal TNF-α expression.

Key words: Primary biliary cholangitis, Splenectomy, Liver fibrosis, Transforming growth factor-β1, Mice