Arai M, Niioka M, Maruyama K, Wada N, Fujimoto N, Nomiyama T, Tanaka S, Okazaki I
Department of Community Health, School of Medicine, Tokai University, Kanagawa, Japan.
Dig Dis Sci. 1996 May;41(5):995-1000. doi: 10.1007/BF02091543.
We treated 18 patients with chronic hepatitis C by recombinant interferon-alpha (6 MIU for 24 weeks). In seven patients, serum aminotransferase levels declined to normal (responders). To evaluate the effect of interferon on matrix metalloproteinases (MMPs) and their inhibitors, namely tissue inhibitors of metalloproteinases (TIMPs), the serum levels of these enzymes were determined by enzyme immunoassay (EIA) using a specific monoclonal antibody. In responders, there was a tendency, but not a significant one, towards either an increase in serum MMP 1 levels or a decrease in serum TIMP 1 levels. In contrast, in nonresponders, both a significant decrease in MMP 1 and MMP 3 and a significant increase in TIMP 1 were observed. The number of cases of either increase in serum MMP levels or decreased in serum TIMP levels was significantly larger in responders than in nonresponders. Furthermore, the ratio of MMP 1 to TIMP 1 significantly increased in responders, suggesting that the balance between matrix formation and degradation in hepatic fibrosis tended to move toward degradation. These data indicate that interferon may exert a beneficial effect on hepatic fibrosis in parallel with improvement of aminotransferase activity.
我们用重组α干扰素（6百万国际单位，疗程24周）治疗了18例慢性丙型肝炎患者。7例患者血清转氨酶水平降至正常（应答者）。为评估干扰素对基质金属蛋白酶（MMPs）及其抑制剂即金属蛋白酶组织抑制剂（TIMPs）的影响，使用特异性单克隆抗体通过酶免疫测定法（EIA）测定了这些酶的血清水平。在应答者中，血清MMP 1水平有升高趋势或血清TIMP 1水平有降低趋势，但不显著。相反，在无应答者中，观察到MMP 1和MMP 3显著降低，TIMP 1显著升高。血清MMP水平升高或血清TIMP水平降低的病例数在应答者中显著多于无应答者。此外，应答者中MMP 1与TIMP 1的比值显著升高，提示肝纤维化中基质形成与降解之间的平衡倾向于向降解方向移动。这些数据表明，干扰素可能在改善转氨酶活性的同时对肝纤维化发挥有益作用。
