大鼠脑出血后血肿周围基质金属蛋白酶2和9及其组织抑制剂1的表达  

Expressions and significance of perihematomal matrix metalloproteinase-2,-9 and tissue inhibitor of metalloproteinase-1 in a rat model of intracerebral hemorrhage

作　　者：王庆广[1] 赵辉[2] 崔桂云[3] 陆军[3] 祖洁[3] 沈霞[3] 

机构地区：[1]江阴市人民医院神经内科,江苏214400 [2]徐州市中心医院神经内科 [3]徐州医学院附属医院神经内科

出　　处：《中国脑血管病杂志》2009年第2期79-83,87,共6页Chinese Journal of Cerebrovascular Diseases

基　　金：江苏省高校自然科学研究资助项目(05KJD320229)

摘　　要：目的观察大鼠脑出血后血肿周围组织基质金属蛋白酶2、9（MMP-2、MMP-9）及其组织抑制剂1（TIMP-1）的表达规律,探讨它们与脑出血后脑水肿的关系。方法取成年雄性SD大鼠156只,随机分为假手术组（18只）和脑出血组（138只）,脑出血组再分为出血后1、3、6、12、24、36、48、72h和7d亚组（每组15只）。采用自体血注入法建立大鼠脑出血模型,分别用脑组织伊文思蓝（EB）含量测血-脑屏障通透性,用干-湿重法测定脑组织的含水量,用Western blot法观察血肿周围MMP-2、MMP-9和TIMP-1的表达规律。每组3只大鼠用于透射电镜观察脑组织病理学形态。结果①血肿周围脑组织的含水量和EB含量在造模后1h起开始增高,48h达到高峰,各时点（除外术后7d的脑组织含水量）与假手术组比较,差异均有统计学意义（P〈0.05～0.01）。②在脑出血后1h,同侧基底核MMP-2开始表达,24h达到高峰,48h前各时点与假手术组比较,差异有统计学意义（P〈0.05）,术后48h恢复正常;MMP-9在脑出血后6h开始表达,48h达到高峰,7d前各时点与假手术组比较,差异有统计学意义（P〈0.05）,术后7d恢复正常;TIMP-1在脑出血后12～36h表达降低,与假手术组比较,差异有统计学意义（P〈0.05～0.01）。③同侧基底核脑组织含水量与EB含量（r=0.940,P〈0.01）、MMP-9表达（r=0.913,P〈0.01）、1～24h MMP-2表达（r=0.903,P〈0.05）呈正相关;与1～24hTIMP-1表达（r=-0.922,P〈0.05）呈负相关。EB含量与MMP-2表达呈正相关（r=0.930,P〈0.01）,与1～24hTIMP-1表达呈负相关（r=-0.950,P〈0.05）。④电镜观察显示,大鼠脑出血后48h,基底核区脑组织血管内皮基底膜遭到明显破坏。结论大鼠脑出血后血肿周围组织MMP-2、MMP-9的表达增加而TIMP-1表达减低,使MMPs与TIMPs之间的平衡遭到破坏,基底膜破坏增加,促进脑水肿的形成。Objective To observe the expressive pattern of matrix metalloproteinase-2, -9 （MMP-2, -9） and their tissue inhibitor of metalloproteinase-1 （TIMP-1） in perihematomal tissue after intracerebral hemorrhage （ICH） in rats and to investigate the relationship between them and brain edema following ICH. Methods A total of 150 SD rats were randomly allocated to either sham-operation group （n = 15 ） or ICH group A [ they were redivided into 9 subgroups according to the different time points （n = 15 in each group ） 1- A rat model of ICH was induced by autologous blood injection. The rats were sacrificed at 1,3, 6, 12, 24, 36, 48, 72 hours and day 7 respectively after the procedure. The blood-brain barrier permeability was determined by Evans blue （EB） ; The brain water content was measured by the wet-dry weight method;and the expression pattern of perihematomal MMP-2, MMP-9 and TIMP-1 was detected by Western blot. The data were compared with the sham-operation group. The same amount of isotonic saline was injected at the same site in the rats of the sham-operation group. Another 6 rats were randomly distributed into control group and ICH group B （ n = 3 in each group）. The brain tissues were examined by transmission electron micro- scope. Results （1）The brain water content and EB content in perihematomal tissue began to increase at 1 hour after ICH, and they reached the peak at 48 hours. As compared with the sham-operation group at different time points （except brain water content at d 7 after the procedure）, there were significant differences （P 〈0.05 -0.01 ）. （2）The MMP-2 in ipsilateral basal ganglia began to express at 1 hour after ICH, and it reached the peaked at 24 hours. As compared with the sham-operation group at different time points before 48 hours, there were significant differences （P 〈 0.05 ）. It returned to normal at 48 hours after the procedure. The MMP-9 began to express at 6 hours after ICH, and it reached the peaked at 48 hours. As compared with the sha

关 键 词：脑出血 脑水肿 明胶酶A 明胶酶B 金属蛋白酶1组织抑制剂 大鼠 

分 类 号：R743.34[医药卫生—神经病学与精神病学] R363[医药卫生—临床医学]