CAJ | 학술논문

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IκB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β-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-κB,从而导致有活性的MMP-9表达增高,使AVM出血风险增加.
목적 탐토염증반응인자급금속기질단백매(MMP)-9재뇌동정맥기형출혈궤제중적작용.방법 (1)실험조:조직급혈액표본래자2010년10월1일지2011년10월1일북경천단의원수치적31례뇌동정맥기형환자,기중출혈조14례,미출혈조17례.(2)대조조:조직표위30례동기천단의원접수섭협절제술적전간환자,혈액표본위30명건강적체검자.용ELISA 방법검측혈장중백세포개소(IL)-6표체.Western단백인적검측조직중핵전록인자NF-κB화IκB이급MMP-9단백수평적표체.채용면역형광방법분별검측각조중적MMP-9적표체,명효매보검측조직중유활성적MMP-2화MMP-9적표체.결과 출혈조환자혈액중IL-6함량(33.2±4.8)ng/L,대조조(15.6±1.0) ng/L,량자비교P＜0.01.MMP-9단백미출혈조1.20±0.35(단위위MMP-9화β-기동단백분자량적비치,하동),대조조위0.34±0.07,량자비교P＜0.05이현시MMP-9적활성적명효매보중,출혈조(0.98±0.07)명현고우대조조(0.30 ±0.07,P ＜0.01).출혈조유활성적MMP-2적표체동양명현고우미출혈조화대조조.결론 IL-6재뇌동정맥기형환자혈장중표체증고,격활료핵전록인자NF-κB,종이도치유활성적MMP-9표체증고,사AVM출혈풍험증가.
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-κB (NF-κB),IκB 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 nonruptured 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 β-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.