基质金属蛋白酶-9及组织基质金属蛋白酶抑制剂-1在脑动静脉畸形组织中的表达及其与出血的关系

Expression of MMP-9,TIMP-1 in Tissue of CAVM and Their Relationship with Hemorrhagic History in CAVM

目的 研究基质金属蛋白酶-9（matrix metalloproteinase-9，MMP-9）及组织基质金属蛋白酶抑制剂-1（tissue inhibitors of metalloproteinasel，TIMP-1）在脑动静脉畸形（cerebuilar arteriovenous malformations，CAVM）患者组织中的表达及其与出血的关系。 方法 选取我院2007年5月至2008年9月间收治的48例CAVM患者。按有无出血症状分为出血组和非出血组，并选取24例原发癫痫患者为正常对照组。分别对其病史、临床症状、影像学表现等进行研究。对患者术中脑组织标本的MMP-9、TIMP-1含量以免疫组化方法进行研究。 结果 MMP-9、TIMP-1均表达在胞浆中。MMP-9在正常对照组仅见微量表达；而在CAVM患者组织标本中可见表达明显升高。TIMP-1在CAVM患者组织中表达水平显著高于对照组，与MMP-9表达平行，出血组组与非出血组之间MMP-9、TIMP-1均无统计学差异，但两者之比（MMP-9／TIMP-1）有统计学差异。 结论 ①MMP-9可能是导致CAVM血管壁结构不稳定、生长和过度扩张的重要因素，其水平升高可能是TIMP-1表达的促进因素之一；②MMP-9可能对于CAVM患者的出血具有促进作用，TIMP-1有着抑制MMP-9活性的重要作用，是防止CAVM出血的“保护因子”。MMP-9和TIMP-1比例失衡，造成MMP-9相对“过盛”，可能是引起脑动静脉畸形出血的重要机制。

Objective To examine the expression of matrix metalloproteinase-9 （MMP-9） and tissue inhibitors of metalloproteinasel（TIMP-1） in cerebullar arteriovenous malformations （CAVM） and their relationship with hemorrhagic history in CAVM. Methods 48 patients who suffered with CAVM were studied, including 24 patients with hemorrhagic history （CAVM H group） and 24 patients without hemorrhagic history （CAVM N group）. 24 patients suffered with essential epilepsy were control group （CG）. All of the patients admitted during May 2007-September 2008 and were given operation. We studied their history, clinical symptom and radiologic manifestation, examined the expression of MMP-9, TIMP-1 in patients brain tissue by immunohistochemistry. Results Compared with control samples, CAVM samples had higher levels of MMP-9, TIMP- 1（P〈0.01）.There was no significant difference in levels of MMP-9, TIMP-1（P〉0.05） between CAVM H Group and CAVM N Group, But, Compared with CAVM N Group, CAVM H Group had higher levels of MMP-9/TIMP-1（P〈0.05）. Conclusion ①Maybe MMP-9 is a essential factor lead to structural instability, growth and abnormal extension of vessels in CAVMs. MMP-9 is one of the factors to promote expression of TIMP-1. ②MMP-9 can lead hemorrhage in CAVMs, as the endogenous specific inhibitor of MMP-9, TIMP-1 is a protective factor to prevent hemorrhage in CAVMs.Perhaps disbalance of MMP-9 and TIMP-1, MMP-9 is higher relatively is a important reason of hemorrhage in CAVMs.