Department of Neurology, Glostrup Hospital, Danish Headache Centre, Copenhagen, Denmark.
Cephalalgia. 2010 Mar;30(3):303-10. doi: 10.1111/j.1468-2982.2009.01954.x. Epub 2010 Feb 1.
To test the hypothesis that permeability of the blood-brain barrier (BBB) is altered during migraine attack due to enhanced activation of matrix metalloproteinases (MMPs), we investigated MMP-3, MMP-9 and tissue inhibitor of metalloproteases (TIMP)-1 in the external jugular vein during and outside of migraine attacks in 21 patients with migraine without aura. In addition, we measured plasma levels of several other proteins including MMP-7, -8, -10 and TIMP-2. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study plasma concentration of MMPs. There was no difference in MMP-9 and TIMP-1 levels between ictal and interictal periods. We found significantly decreased plasma levels of MMP-3 in the external jugular (P = 0.002) and cubital (P = 0.008) vein during attacks compared with outside of attacks. We found no correlation of ictal or interictal MMP-3, MMP-9 and TIMP-1 to migraine duration and frequency analysed in 21 patients (P > 0.05). There was no difference between ictal and interictal plasma levels of MMP-7, -8, -10 and TIMP-2 (P > 0.05). Our data suggest that plasma MMP-9 cannot be used as a biomarker of BBB disruption in migraine without aura. Decreased MMP-3 levels are an interesting and unexpected finding warranting further investigation.
为了验证偏头痛发作期间血脑屏障（BBB）通透性因基质金属蛋白酶（MMPs）的激活而改变的假说，我们在 21 例无先兆偏头痛患者偏头痛发作期间和发作间期在外颈静脉中检测了 MMP-3、MMP-9 和金属蛋白酶组织抑制剂（TIMP）-1。此外，我们还测量了几种其他蛋白，包括 MMP-7、-8、-10 和 TIMP-2 的血浆水平。我们使用基于规则的医学多分析物分析和蛋白质阵列技术研究 MMP 的血浆浓度。在发作期间和发作间期，MMP-9 和 TIMP-1 水平无差异。与发作间期相比，我们发现发作期间外颈静脉（P=0.002）和肘静脉（P=0.008）中 MMP-3 的血浆水平显著降低。我们发现，在 21 例患者中，发作期间和发作间期的 MMP-3、MMP-9 和 TIMP-1 与偏头痛持续时间和频率均无相关性（P＞0.05）。发作期间和发作间期的 MMP-7、-8、-10 和 TIMP-2 血浆水平无差异（P＞0.05）。我们的数据表明，血浆 MMP-9 不能作为无先兆偏头痛 BBB 破坏的生物标志物。MMP-3 水平降低是一个有趣且意外的发现，值得进一步研究。
