脾切除对原发性胆汁性肝硬化小鼠肝组织纤维化影响研究*

目的 探讨脾切除对原发性胆汁性肝硬化（PBC）小鼠的影响及其相关因素。方法 40只雌性C57BL/6小鼠被分为脾切除组（n=10）、假手术组（n=10）、模型组（n=10）和正常对照组（n=10）。在前三组,采用1%聚肌胞苷酸腹腔注射建立PBC模型,在正常对照组,给予等体积生理盐水腹腔注射。在实验20 w末,对动物分别行脾切除术,或在假手术组采取腹壁切开后仅轻微翻动脾脏,或在模型组和正常对照组不行任何处理。在实验32w,行血生化和肝组织病理学检查。采用RT-PCR法检测肝组织转化生长因子-β1（TGF-β1）及其I型受体（TβRI）和II型受体（TβRII）mRNA水平。取末端回肠组织,采用ELISA法检测其匀浆TNF-α水平。结果 在32w时,脾切除组、假手术组和模型组动物肝指数均显著低于对照组（41.5±5.2）、（39.6±7.5）、（39.1±1.0）对（53.2±2.1),P值均<0.05];脾切除组血清ALT、AST和ALP水平分别为（43.5±6.4） U/L、（157.7±20.9） U/L和（178.1±38.0）U/L,显著低于模型组（52.0±9.0） U/L、（183.4±12.4） U/L和（195.3±62.6） U/L,P值均<0.05];脾切除组肝组织纤维化程度明显轻于假手术组和模型组;脾切除组肝组织TGF-β1、TβRI和TβRII mRNA水平分别为（0.5±0.09）、（0.5±0.05）和（0.5±0.09）,显著低于模型组（1.0±0.10）、（1.0±0.08）和（1.0±0.09）,P值均<0.05];脾切除组回肠末端匀浆TNF-α水平为（50.0±8.6） ng/L,显著低于模型组 （106.8±19.8） ng/L,P<0.05]。结论 脾切除可缓解PBC小鼠肝组织纤维化进程,可能与抑制肝脏TGF-β1表达和抑制回肠末端TNF-α分泌有关。

Effects of splenectomy on hepatic fibrosis in mice with poly I:C-induced primary biliary cirrhosis

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.