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【摘要 】 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。
The effect of cellular factors on hepatic fibrosis in mice with schistosomiasis japonica He Yongwen, Liu Wei. Department of Infectious Diseases, Xiehe Hospital, Tongji Medical University, Wuhan 430022
【 Abstract 】 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.
【 Key words 】 Schistosomiasis japonica Liver cirrhosis Tumor necrosis factor Interleukin-1
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