肝纤维化时胶原降解酶活性变化的研究

COLLAGENOLYTIC ENZYME ACTIVITY IN EXPERIMENTAL HEPATIC FIBROSIS

通过溶液法检测不同肝纤维化时期鼠肝组织匀浆胶原酶（ｃｏｌｌａｇｅｎａｓｅ）的活性变化，以及血清Ｎ－乙酰β－Ｄ氨基葡萄糖苷酶（β－ＮＡＧ）和甘氨酰脯氨西酸二肽酶（ＧＰＤＡ）的活性变化，结合电镜和免疫组化等方法，观察肝纤维化时胶原降解酶活性变化与肝组织病理关系。结果显示随着肝纤维化病程的进展，胶原酶的活性在肝纤维化进入肝硬化的活动期状态较正常对照组有明显增高（Ｐ＜０．０５），而β－ＮＡＧ和ＧＰＤＡ在肝纤维化过程中活性以肝纤维化早期最明显（改正常对照分别为Ｐ＜０．０５和Ｐ＜０．０１）。同时组织病理也随着病程进展，Ⅰ、Ⅲ、Ⅳ型胶原在肝内沉积，肝窦基底膜破坏，连续性基底膜的形成都与胶原降解酶的活性变化密切相关。

Collagenolytic enzyme activities including histo-collagenase and serum beta-N-acetylhexosaminidase (β-NAG), glycylproline-prolyldipeptidyl-aminopeptidase(GPDA) were measured in different periods of rat hepatic fibrosis, and co-analysed with development of hepatic pathologic histology. Wistar rats(>150g) were injected twice weekly with CCl40.3ml/100g in mineral oil (33% v/v).Interstitial collagenase activities were measured in homogenate from rat liver samples following acute injury(3 weeks) ; early stage (6 weeks), late stage (10 weeks), and of normal rats. β-NAG and GPDA were determined parallelly in serum. The results suggested that collagenase activities increased significantly in late stage of hepatic fibrosis(P<0.05). Activities of β-NAG and GPDA increased significantly in early stage of hepatic fibrosis(P<0.05 and P<0.01, respectively). Pathologic histology suggested that desposition of type Ⅰ、Ⅲ、Ⅳ collagen may lead to the development of identifiable basement membranes in the Disse space and defenstration of the endothelial cells, as so called sinusoidal capillarization. These data suggest that collagenase,β-NAG and GPDA may play an important role in collagen accumulation in hepatic fibrosis.