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Analysis of liver fibrosis in schistosomiasis

血吸虫病肝纤维化分析

基本信息

批准号：
04670235
负责人：
TANABE Masanobu
金额：
$ 1.34万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670235/
关键词：
Schistosoma mansoni Liver fibrosis Collagen synthesis Procollagen mRNA Snthetic anionic polymer Cell-free protein synthesis Hepatocyte Fibroblast

项目摘要

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.

在各种阴离子聚合物和/或多离子络合物中，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，用HOMO-AP处理的小鼠被用来纯化纤维化因子。虽然未能成功从肝提取液中分离纯化致纤维化因子，但经DEAE离子交换层析和凝胶过滤后，可从经Homo-AP处理的曼氏血吸虫感染小鼠的虫卵肉芽肿培养上清液中部分纯化成纤维细胞因子。感染后第7~11周，宿主对血吸虫虫卵的肉芽肿性反应最为明显，此时肝脏胶原蛋白迅速增加。在此期间，感染组小鼠肝脏前胶原mRNA和游离脯氨酸含量及体外胶原合成活性均显著高于未感染对照组。感染12周后，肝胶原蓄积速度急剧变慢。胶原蛋白堆积发生如此剧烈变化的确切原因尚不清楚。感染12周后，感染组小鼠肝脏前胶原mRNA水平和体外胶原合成活性显著升高，而肝组织游离脯氨酸浓度下降至未感染对照组水平。此外，肝切片体外合成胶原的活性依赖于游离脯氨酸的浓度。因此，肝脏游离脯氨酸可能在血吸虫病肝纤维化的发病机制中起主要作用。