Suppression of MMP-9 by doxycycline in brain arteriovenous malformations.
Suppression of MMP-9 by doxycycline in brain arteriovenous malformations.
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DOI：
10.1186/1471-2377-5-1
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发表时间：
2005-01-24
期刊：
影响因子：
2.6
通讯作者：
University of California, San Francisco, BAVM Study Group
中科院分区：
文献类型：
--
作者：
Hashimoto T;Matsumoto MM;Li JF;Lawton MT;Young WL;University of California, San Francisco, BAVM Study Group
本研究的主要目的是证明利用强力霉素抑制脑动静脉畸形（AVM）中基质金属蛋白酶-9（MMP-9）的可行性。AVM组织的离体处理：用多西环素处理完整AVM组织48小时。测定培养基中的活性和总MMP-9。初步试验：AVM患者在AVM切除术前接受强力霉素（100 mg）或安慰剂，每日两次，持续一周。检测BVM组织中活性MMP-9和总MMP-9的含量。AVM组织的离体处理：10和100 μg/ml的多西环素显著降低了离体AVM组织中的MMP-9水平（总：对照vs 10 vs 100 μg/ml = 100 ± 6 vs 60 ± 16 vs 61 ± 9%;活性：100 ± 8 vs 48 ± 16 vs 59 ± 10%）。初步试验：10例患者接受强力霉素，4例患者接受安慰剂。多西环素组的MMP-9水平有低于安慰剂组的趋势（总量：2.18 ± 1.94 vs 3.26 ± 3.58，P = 0.50;活性：0.48 ± 0.48 vs 0.95 ± 1.01 ng/100 μg蛋白，P = 0.25）。临床相关浓度的强力霉素降低了离体AVM组织中的MMP-9。此外，有一种趋势，口服强力霉素短至一周导致AVM组织中MMP-9的降低。进一步的研究是必要的，以证明临床试验，以测试多西环素对MMP-9的表达在AVM组织的影响。
The primary aim of this study is to demonstrate the feasibility of utilizing doxycycline to suppress matrix metalloproteinase-9 (MMP-9) in brain arteriovenous malformations (AVMs). Ex-vivo treatment of AVM tissues: Intact AVM tissues were treated with doxycycline for 48 hours. Active and total MMP-9 in the medium were measured. Pilot trial: AVM patients received either doxycycline (100 mg) or placebo twice a day for one week prior to AVM resection. Active and total MMP-9 in BVM tissues were measured. Ex-vivo treatment of AVM tissues: Doxycycline at 10 and 100 μg/ml significantly decreased MMP-9 levels in AVM tissues ex-vivo (total: control vs 10 vs 100 μg/ml = 100 ± 6 vs 60 ± 16 vs 61 ± 9%; active: 100 ± 8 vs 48 ± 16 vs 59 ± 10%). Pilot trial: 10 patients received doxycycline, and 4 patients received placebo. There was a trend for both MMP-9 levels to be lower in the doxycycline group than in the placebo group (total: 2.18 ± 1.94 vs 3.26 ± 3.58, P = .50; active: 0.48 ± 0.48 vs 0.95 ± 1.01 ng/100 μg protein, P = .25). A clinically relevant concentration of doxycycline decreased MMP-9 in ex-vivo AVM tissues. Furthermore, there was a trend that oral doxycycline for as short as one week resulted in a decrease in MMP-9 in AVM tissues. Further studies are warranted to justify a clinical trial to test effects of doxycycline on MMP-9 expression in AVM tissues.
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