Isolation and Characterization of Biological Active Materials from Fish Skin Waste

在海洋食品工业中，鱼皮像骨头和内脏一样被当作废物丢弃，这些废物占整个体重的一半以上，希望在其他一些产品中得到利用。鱼皮约占鱼类废物的10%，可以机械去除，并在食品加工中很容易回收。大比目鱼（Reinhararditus hippoglossoides）的皮肤是日本鸟取县主要的海洋食品加工产品，含有34%的蛋白质和相关物质，14%的油和52%的水。利用这种鱼皮有望促进当地工业的发展。顺便提一下，据报道，肝炎、肝硬化和肝癌等肝脏疾病最近在日本中年劳动一代中呈现出迅速增加的趋势。它也成为治疗性或改良性药物急需开发的重要课题。本课题首先以鱼皮为原料，建立了胶原蛋白和细胞外基质成分的提取纯化工艺。作为鱼类胶原蛋白的应用，我们成功地进行了原代肝细胞的三维培养，并发现在这种培养中肝功能得到了很好的维持。此外，我们还发现鱼皮蛋白多糖粗提物在培养细胞中具有显著的HGF诱导作用。在分离得到的糖胺聚糖中，鱼皮中糖胺聚糖的主要成分硫酸皮聚糖对HGF的诱导活性最强。由于牛胶原蛋白的使用被限制用于感染引起疯牛病和克雅氏病的朊病毒，因此应该重新评估鱼胶原蛋白的重要性。

In the marine food industry, fish skin is discarded as waste like bone and entrails, and these waste materials make-up more than a half of the whole body weight, desired for utilization in some other products. The skin of fish, which is composed of about 10% of fish waste, can be mechanically removed and readily recovered in food processing. The skin of a halibut Reinhararditus hippoglossoides, which is a main marine-food processing product in Tottori Prefecture Japan, contains 34% protein and related materials, 14% oil, and 52% water. The utilization of this fish skin is expected to contribute the development of local industry. Incidentally, liver diseases, such as hepatitis, liver cirrhosis and hepatoma were reported to show a tendency of rapid increase recently within Japanese people in the working generation of middle ages. It has also become an important subject to be urgently developed for therapeutic or ameliorative medication. At first in this project, the extraction and puriflcation process of collagen and extracellular matrix components were established using fish skin. As the application of fish collagen, we have succeeded the three dimensional culture of primary hepatocytes, and revealed that liver function was well maintained in this culture. Furthermore, we showed that proteoglycan crude extracts from the fish skin has significant inducibility of HGF in culture cell. Especially, of the separated glycosaminoglycans, dermatan sulfate which was the main component of glycosaminoglycans in the fish skin, showed the strongest activity in HGF induction. As the use of cattle collagen is restricted for the infection of the prion that is the cause of BSE and the Creutzfeldt-Jakob disease, the importance of fish collagen should be re-evaluated.