Ljumovic Dusanka, Diamantis Ioannis, Alegakis Athanasios K, Kouroumalis Elias A
Liver Research Laboratory University of Crete Medical School, 71003 Heraklion, Crete, Greece.
Clin Chim Acta. 2004 Nov;349(1-2):203-11. doi: 10.1016/j.cccn.2004.06.028.
Fibrosis is a common consequence of chronic liver diseases irrespective of aetiology. Metalloproteinases play an important role in the fibrotic process participating in the balance between collagen synthesis and degradation. We examined whether matrix gelatinases and stromelysins are similarly involved in the development of viral (HCV, HBV) and non-viral (NASH) liver diseases.
Hepatic mRNA levels of matrix metalloproteinase MMP-2, MMP-9, MMP-10 and MMP-11 isolated from liver biopsies were measured by semi-quantitative RT-PCR. Seventy-three patients were examined in this study: non-diseased controls (10), patients with chronic hepatitis B (14), chronic hepatitis C (33) and non-alcoholic steatohepatitis (16).
A significant increase of MMP-9 and MMP-10 expression was found in patients with non-viral (non-alcoholic steatohepatitis) liver disease. Patients with chronic hepatitis B and hepatitis C showed an increase in MMP-2 mRNA expression compared to controls. Moreover, chronic hepatitis B and hepatitis C patients had significantly different mRNA expression patterns.
These findings indicate that matrix metalloproteinases are differentially involved in the fibrotic process of viral and non-viral chronic liver diseases. Differences exist between HBV and HCV chronic hepatitis. Differences between early and late fibrosis indicate that in future studies, careful staging of patients is mandatory for interpretation of results.
纤维化是慢性肝病常见的后果，与病因无关。金属蛋白酶在纤维化过程中发挥重要作用，参与胶原蛋白合成与降解的平衡。我们研究了基质明胶酶和基质溶素是否同样参与病毒性（丙型肝炎病毒、乙型肝炎病毒）和非病毒性（非酒精性脂肪性肝炎）肝病的发展。
通过半定量逆转录聚合酶链反应测量从肝活检中分离出的基质金属蛋白酶MMP-2、MMP-9、MMP-10和MMP-11的肝脏mRNA水平。本研究共检查了73例患者：非患病对照者（10例）、慢性乙型肝炎患者（14例）、慢性丙型肝炎患者（33例）和非酒精性脂肪性肝炎患者（16例）。
在非病毒性（非酒精性脂肪性肝炎）肝病患者中发现MMP-9和MMP-10表达显著增加。与对照相比，慢性乙型肝炎和丙型肝炎患者的MMP-2 mRNA表达增加。此外，慢性乙型肝炎和丙型肝炎患者的mRNA表达模式有显著差异。
这些发现表明，基质金属蛋白酶以不同方式参与病毒性和非病毒性慢性肝病的纤维化过程。乙型肝炎病毒和丙型肝炎病毒慢性肝炎之间存在差异。早期和晚期纤维化之间的差异表明，在未来的研究中，为了解释结果，对患者进行仔细分期是必要的。
