Lee Sang-Ho, Coger Robin N, Clemens Mark G
Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
Tissue Eng. 2006 Oct;12(10):2825-34. doi: 10.1089/ten.2006.12.2825.
Improvement of O(2) supply in bioartificial liver devices remains a critical issue in maintaining hepatocyte viability and functions. Therefore, the current study investigates whether enhanced oxygen (O(2)) transport through collagen extracellular matrix (ECM) can produce a more stable antioxidant defense in different O(2) tensions during prolonged incubation times. Total glutathione concentration of cultured hepatocytes in enhanced ECM was significantly higher than in normal ECM under the lowest O(2) tension phase (2.60mm of thickness from O(2) source), and was also significantly increased in 0.52 mm transport distance of hypoxia as compared to normoxic conditions. Catalase and glutathione reductase activities for hepatocytes within enhanced ECM were also significantly preserved relative to their values for the normal collagen ECM. Specifically, the enhanced ECM produced higher activities at a further transport distance (1.56 mm) from the O(2) source at the 24 h time-point, and remained higher up to the 96 h incubation time. In contrast, the glutathione peroxidase activities in both collagen ECM systems were similar. Hepatocyte viability in the enhanced ECM system was also consistently greater than that for normal ECM. These results suggest that the O(2) enhanced collagen ECM preserves the antioxidant defense system as compared to normal collagen ECM, ostensibly via increased micropathways for O(2) transport to the hepatocytes.
在生物人工肝装置中改善氧气(O₂)供应仍然是维持肝细胞活力和功能的关键问题。因此,本研究探讨了在延长培养时间的不同氧气(O₂)张力下,通过胶原蛋白细胞外基质(ECM)增强氧气(O₂)运输是否能产生更稳定的抗氧化防御。在最低氧气(O₂)张力阶段(距氧气(O₂)源2.60毫米厚度处),培养于增强型ECM中的肝细胞总谷胱甘肽浓度显著高于正常ECM中的肝细胞,并且与常氧条件相比,在缺氧0.52毫米运输距离处也显著增加。相对于正常胶原蛋白ECM中的肝细胞,增强型ECM中肝细胞的过氧化氢酶和谷胱甘肽还原酶活性也显著保持。具体而言,在24小时时间点,增强型ECM在距氧气(O₂)源更远的运输距离(1.56毫米)处产生了更高的活性,并且在长达96小时的培养时间内一直保持较高水平。相比之下,两种胶原蛋白ECM系统中的谷胱甘肽过氧化物酶活性相似。增强型ECM系统中的肝细胞活力也始终高于正常ECM中的肝细胞活力。这些结果表明,与正常胶原蛋白ECM相比,氧气(O₂)增强的胶原蛋白ECM通过增加向肝细胞运输氧气(O₂)的微通道,表面上保留了抗氧化防御系统。