Analysis of liver fibrosis in schistosomiasis

在各种类型的阴离子聚合物和/或聚离子复合物中，丙烯酸均聚物（HOMO-AP）单独具有刺激血吸虫病肝纤维化的作用。因此，施用HOMO-AP的小鼠用于纯化纤维化因子。虽然从肝提取液中不能成功纯化纤维化因子，但通过离子交换层析和凝胶过滤，可以从曼氏血吸虫感染小鼠的虫卵肉芽肿培养液中部分纯化纤维化因子。肝胶原在感染后第7 ~ 11周迅速增加，此时宿主对组织虫卵的肉芽肿反应最为显著。在此期间，肝前胶原mRNA和游离脯氨酸的含量，并在体外胶原合成活性在感染小鼠表现出显着高于未感染对照组的值。感染12周后，肝胶原的积累速度明显减慢。胶原蛋白积累发生如此剧烈变化的确切原因仍不清楚。感染12周后，小鼠肝组织前胶原mRNA水平和体外胶原合成活性明显升高，但肝组织游离脯氨酸浓度下降至未感染对照组水平。肝片体外胶原合成活性与游离脯氨酸浓度有关。因此，肝游离脯氨酸可能在血吸虫病肝纤维化的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.