细胞因子对感染日本血吸虫小鼠肝纤维化的影响

The effect of cellular factors on hepatic fibrosis in mice with schistosomiasis japonica

目的探索细胞因子对日本血吸虫病肝纤维化的影响。方法用免疫组化技术，观察１１０只昆明鼠（其中９０只为感染日本血吸虫鼠）肝内肿瘤坏死因子（ＴＮＦ）α和细胞外基质的量及分布，和注射ＴＮＦ及白细胞介素（ＩＬ）１后它们的变化。结果感染后１２周小鼠肝内ＴＮＦ达高峰，主要分布在虫卵肉芽肿内及其周围。纤维连接素、层连素、Ⅰ及Ⅲ型胶原分别于感染后１６及２０周达高峰，由细线状增宽变厚，呈条索状沉积在肉芽肿内及其周围。注射ＴＮＦ后，感染鼠肝内Ⅰ型胶原明显增加（Ｐ＝００１）；注射ＩＬ１使Ⅰ及Ⅲ型胶原略多于同期未注射组；联合注射ＴＮＦ和ＩＬ１，肝内ＴＮＦ及Ⅰ型胶原显著高于同期非注射组（Ｐ＜００５，Ｐ＝００１）。结论ＴＮＦ可刺激昆明鼠肝内胶原增加，ＩＬ１具有协同ＴＮＦ的作用。

Objective To probe the effect of tumor necrosis factor α (TNF α) and interleukin 1 (IL 1) on extracellular matrix in the liver of mice with schistosomiasis japonica. Methods The amount and distribution of TNF α and extracellular matrix in liver of 90 infected mice and 20 controls and the change of extracellular matrix after administration of TNF α and IL 1 were determined with streptavidin biotin peroxidase complex method. Results The amount of TNF α in the liver began to rise obviously 8 weeks after infection, peaked 16 weeks after infection (9 mice reached 2+～4+ grade), and was mainly distributed in and a round the egg granuloma. Fibronectin (FN), laminin (LN), type Ⅰ and Ⅲ collagen in the liver began to rise 8 weeks after infection and were lineally distributed around the egg granuloma. They peaked respectively 16 and 20 weeks after infection (over 70% infected mice reached 3+～4+ grade), became wide, thick and retiform, and deposited around and in the egg granuloma. After administration of recombinant TNF α to the infected mice, the changes of the amount of TNF, FN, laminin (LN), and type Ⅲ collagen in the liver were insignificant, and only the amount of type Ⅰ collagen was significantly higher ( P =0 01) than that in the untreated group at the same stage. After injection of IL 1, there was little effect on TNF, FN and LN, while type Ⅰ and Ⅲ collagen were slightly higher than those in the untreated group at the same stage, indicating that its effect was inferior to TNF. After injection of TNF α in combination with IL 1. The amount of TNF and type Ⅰ collagen in the liver of infected mice rose notably, being significantly higher than those in the untreated group ( P <0.05, P =0.01). Conclusion TNF may play a role in stimulation of fibroblast in the liver to proliferate and resulted in an increase of extracellular matrix. IL 1 assisted TNF α during this course and promoted the formation of hepatic fibrosis.