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=001);注射IL1使Ⅰ及Ⅲ型胶原略多于同期未注射组;联合注射TNF和IL1,肝内TNF及Ⅰ型胶原显著高于同期非注射组(P<005,P=001)。结论TNF可刺激昆明鼠肝内胶原增加,IL1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.
出处
《中华内科杂志》
CAS
CSCD
北大核心
1998年第4期259-261,共3页
Chinese Journal of Internal Medicine
基金
卫生部科学基金