Analysis of liver fibrosis in schistosomiasis

在各种阴离子聚合物和/或多离子复合物中，仅丙烯酸均聚物（HOMO-AP）具有刺激血吸虫病肝纤维化的作用。因此，用HOMO-AP对小鼠进行纤维原性因子的纯化。虽然不能从肝提取物中纯化纤维原性因子，但经DEAE离子交换层析和凝胶过滤，可从经HOMO-AP处理的mansoni感染小鼠的鸡蛋肉芽肿培养基中部分纯化纤维原性因子。小鼠曼氏血吸虫病肝纤维化涉及鸡蛋肉芽肿上胶原纤维的过度沉积。肝胶原蛋白在感染后第7 ~ 11周迅速增加，此时宿主对血吸虫卵的肉芽肿反应最为明显。在此期间，感染小鼠的肝脏前胶原mRNA和游离脯氨酸含量以及体外胶原合成活性均显著高于未感染小鼠。感染12周后，肝胶原蛋白的积累速度急剧变慢。胶原蛋白积累发生如此剧烈变化的确切原因尚不清楚。感染12周后，感染小鼠肝脏前胶原mRNA和体外胶原合成活性均升高，但肝脏游离脯氨酸浓度降至未感染对照组水平。肝片体外合成胶原的活性与游离脯氨酸的浓度有关。因此，肝游离脯氨酸可能在血吸虫病肝纤维化机制中发挥重要作用。

Among various types of anionic polymers and/or poly-ion-complex, homopolymer of acrylic acid (HOMO-AP) alone had an action to stimulate the liver fibrosis in schistosomiasis. Therefore, the mice administered with HOMO-AP were utilized for the purification of fibrogenic factor. Although the purification of fibrogenic factor from liver extract could not succeed, it could be partially purified from the culture medium of egg granulomas isolated from S.mansoni-infected mice treated with HOMO-AP by DEAE ion-exchange chromatography and gel filtration.Hepatic fibrosis in murine schistosomiasis mansoni involve the excessive deposition of collagen fiber on the egg granulomas. The hepatic collagen incereased rapidly during the 7th to 11th weeks of infection, when host granulomatous response against shistosome eggs was most prominent. During this period, hepatic contents of procollagen mRNA and free proline, and in vitro collagen-synthetic activity in the infected mice showed a significantly higher values than those of uninfected controls. After the 12th week of infection, the accumulation rate of hepatic collagen drastically changed to much more slowly. The exact reason of such a drastic change in collagen accumulation remains unknown. High level of hepatic procollage mRNA and in vitro collagen sythetic activity were demonstrated in the infected mice after the 12th week of infection, but hepatic free proline concentration decreased to the level of uninfected controls. Moreover, the activity of in vitro collagen synthesis by liver slice was dependent on the concetnration of free proline. It is, therefore, likely that hepatic free proline may play a major role in the mechanism of liver fibrosis in schistosomiasis.