Pérez-Tamayo R, Montfort I
Am J Pathol. 1980 Aug;100(2):427-42.
The susceptibility of hepatic collagen to homologous collagenase in human and experimental CCl4 cirrhosis of the liver has been explored in vitro by exposure of cryostat liver sections to the corresponding enzymes for different time periods. The morphology and extent of collagen degradation was studied by the Picrosirius red/polarizing microscopy technique. The results of various experiments indicate that collagen present in cryostat sections of both human and rat normal and cirrhotic livers is resistant to trypsin digestion for periods of exposure of up to 48 hours but that heating the sections to 60 C for 1 hour renders the collagen susceptible to degradation by trypsin. Incubation of cryostat liver sections with bacterial collagenase revealed progressive degradation of collagen with a uniform pattern of changes in the original color and diameter of the fibers. Exposure of liver sections to homologous collagenases gave rise to the same pattern of changes observed with bacterial collagenase, although less extensive when equal incubation periods were compared. Nevertheless, sufficiently prolonged incubation of liver sections with their homologous collagenases eventually showed degradation of all collagen present in all normal and cirrhotic liver sections. These observations suggest that in the presence of non rate-limiting concentrations of homologous collagenase, the susceptibility of hepatic collagen to the corresponding degrading enzyme is probably not responsible for the irreversibility of the disease.
通过将低温恒温器肝脏切片暴露于相应酶不同时间段，在体外研究了人类和实验性四氯化碳性肝硬化肝脏中肝胶原对同源胶原酶的敏感性。采用天狼星红/偏振显微镜技术研究了胶原降解的形态和程度。各种实验结果表明，人类和大鼠正常及肝硬化肝脏低温恒温器切片中的胶原，在长达48小时的暴露时间内对胰蛋白酶消化具有抗性，但将切片加热至60℃1小时会使胶原易于被胰蛋白酶降解。用细菌胶原酶孵育低温恒温器肝脏切片显示胶原逐渐降解，纤维的原始颜色和直径呈现一致的变化模式。将肝脏切片暴露于同源胶原酶也产生了与细菌胶原酶观察到的相同变化模式，尽管在比较相同孵育时间时程度较轻。然而，用同源胶原酶对肝脏切片进行足够长时间的孵育最终显示，所有正常和肝硬化肝脏切片中存在的所有胶原均发生降解。这些观察结果表明，在同源胶原酶非限速浓度存在的情况下，肝胶原对相应降解酶的敏感性可能不是该疾病不可逆性的原因。
