人日本血吸虫性大肠纤维化胶原蛋白和细胞因子观察

Observation on collagens and cytokines of human large intestinal fibrosis of patients with Schistosoma japonicum infection

目的观察日本血吸虫病传播阻断后人大肠纤维化胶原蛋白和细胞因子的改变。方法在日本血吸虫病传播阻断达标10年地区收集102例血吸虫感染患者大肠标本,在组织切片上进行Ⅰ-Ⅳ型胶原蛋白以及转化生长因子β1（TGFβ1）、碱性纤维母细胞生长因子（bFGF）、基质金属蛋白酶-1（MMP-1）和基质金属蛋白酶组织抑制剂-1（TIMP-1）的免疫组化染色和定量分析。收集同期51例无血吸虫感染者大肠标本作对照。结果102例血吸虫感染患者大肠肠壁内虫卵均已死亡和钙化。26份标本（25.5%）在死亡和钙化虫卵周围发现肉芽肿反应。虫卵高密度组（〉60个/mm^2）大肠的Ⅰ-Ⅲ型胶原平均吸光度（A）值均较对照组增高,而Ⅳ型胶原平均A值下降。Ⅰ-Ⅲ型胶原平均A值的增加均与肉芽肿反应呈正相关。血吸虫感染大肠肉芽肿组的TGFβ1、bFGF和MMP-1的平均A值分别高于对照组,而TIMP-1的A值低于对照组。结论参与日本血吸虫性大肠纤维化的胶原蛋白和细胞因子含量与虫卵密度、纤维化时期和有无肉芽肿反应有关。

Objective To observe the changes of collagens and cytokines in the human large intestinal fibrosis of patients with Schistosoma japonicum （S. japonicum） infection. Methods The type Ⅰ-Ⅳ collagens, TGFβ1, bFGF, MMP-1, TIMP-1 were immunohistochemically stained and quantified, respectively, in the tissue slides from 102 specimens of human large intestine of patients with S. japonicum infection in the area where schistosomiasis transmission has been interrupted for 10 years. Fifty-one specimens of large intestine of persons without S. japonicum infection were selected as the control. Results All eggs deposited in the wall of intestines of patients with S. japonicum infection were dead and calcified. The granulomatous inflammation around the calcified eggs was found in about 25.5% （26/102） of specimens. The average optical densities （A values） of type Ⅰ-Ⅲ collagens increased and the average A value of type Ⅳ collagen decreased in the group of high egg density compared with the control. There existed a positive correlation between the increase of A values of type Ⅰ-Ⅲ collagens and granulomatous reaction. The average A values of TGFβ1, bFGF and MMP-1 increased and the average A values of TIMP-1 decreased in the granulomatous group compared with the control. Conclusions The egg-related large intestinal fibrosis is a prolonged process after the interruption of schistosomiasis transmission. The contents of collagens and cytokines involved in the fibrosis depend upon the egg density, fibrosis duration and granulomatous reaction.