白细胞介素-6等炎症因子表达在脑动静脉畸形出血中的意义

High expression level of interleukin-6 led to elevated hemorrhagic risk of cerebral arteriovenous malformations

目的探讨炎症反应因子及金属基质蛋白酶（MMP）-9在脑动静脉畸形出血机制中的作用。方法（1）实验组：组织及血液标本来自2010年10月1日至2011年10月1日北京天坛医院收治的31例脑动静脉畸形患者，其中出血组14例，未出血组17例。（2）对照组：组织标为30例同期天坛医院接受颞叶切除术的癫痫患者，血液标本为30名健康的体检者。用ELISA方法检测血浆中白细胞介素（IL）-6表达。Western蛋白印迹检测组织中核转录因子NF-κB和IKB以及MMP-9蛋白水平的表达。采用免疫荧光方法分别检测各组中的MMP-9的表达，明胶酶谱检测组织中有活性的MMP-2和MMP-9的表达。结果出血组患者血液中IL-6含量（33．2±4．8）ng／L，对照组（15．6±1．0）ng／L，两者比较P〈0．01。MMP-9蛋白未出血组1．20±0．35（单位为MMP-9和B-肌动蛋白分子量的比值，下同），对照组为0．34±0．07，两者比较P〈0．05而显示MMP-9的活性的明胶酶谱中，出血组（0．98±0．07）明显高于对照组（0．30±0．07，P〈0．01）。出血组有活性的MMP-2的表达同样明显高于未出血组和对照组。结论IL-6在脑动静脉畸形患者血浆中表达增高，激活了核转录因子NF-KB，从而导致有活性的MMP-9表达增高，使AVM出血风险增加。

Objective To explore the mechanistic roles of interleukin-6 （IL-6） and matrix metallopeptidase 9 （MMP-9） in cerebral arteriovenous malformation （AVM）. Methods A total of 31 AVM patients were admitted into Beijing Tiantan Hospital from October 1, 2010 to October 1, 2011, including 14 ruptured and 17 non-ruptured ones. Tissue samples were obtained from all 31 patients and 30 epileptics undergoing temporal lobectomy. The blood samples were obtained from all 31 patients preoperatively and 30 healthy controls. Western blot was employed to measure transcription factors nuclear factor-KB （NF-KB）, IKB and MMP-9 in tissues. And immunofluorescence was performed to measure the tissue expression of MMP- 9 in each group. Gelatin zymography was used to detect the tissue expressions of activated MMP-9 and MMP- 2. Results The blood levels of IL-6 in the ruptured group were significantly higher than those in the non- ruptured and control groups （33.2± 4. 8 vs 23.8 ± 1.2 ng/L, P 〈 0. 05 ; 33.4 ± 4. 8 vs 15.6 ± 1.0 ng/L, P 〈 0. 01 ）. Protein expression in the non-ruptured group was greater than that in the normal and ruptured groups（ 1.20 ±0. 35 vs 0. 34± 0. 07 ; 1.20 ± 0. 35 vs 0. 31 ± 0. 09, unit： molecular weight ratio of MMP-9 and 13-actin）, and gelatin zymography showed that the activity of MMP-9 was significantly higher in the ruptured than the non-ruptured and control groups （ 0. 98 ± 0. 07 vs 0. 40 ± 0. 09 ; 0. 98 ± 0. 07 vs 0. 30 ± 0. 07, unit：ratio of MMP-9 and standard）. In the ruptured group, active MMP-2 expression was significantly higher than that in the other groups. Conclusion IL-6 may stimulate the transformation of MMP-9 into activated form in ruptured AVM tissues and thus lead to an elevated hemorrhage risk of AVM.