大鼠局灶性脑缺血再灌注后MMP-9、TIMP-1的表达

目的 探讨基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶组织抑制因子-1(TIMP-1)在局灶性脑缺血再灌注中的表达规律.方法 健康雄性Wistar大鼠40只按随机数字表法分为缺血再灌注组(I/R组,共25只)和假手术组(Sham组,共15只).采用线栓法成功制作可复血流的大脑中动脉栓塞(MCAO)模型,缺血2 h后再灌注,于再灌注6 h、24 h、48 h、72 h和7 d时取材,进行MMP-9、TIMP-1免疫组织化学染色,通过免疫组化方法分析MMP-9、TIMP-1表达规律和在脑组织中的分布.结果 在I/R组,MMP-9再灌注6 h即有表达,24 h明显增多,48 h达高峰,72 h下降,7d时有微量的表达;TIMP-1在6h亦有表达,24h达高峰,48h时开始下降,7d时有微量表达.二者的阳性表达部位主要在血管内皮细胞,神经元、小胶质细胞亦有少量表达.Sham组未见阳性结果.结论 脑局部缺血再灌注后可诱导MMP-9、TIMP-1的大量表达,缺血后血管内皮损害是MMP-9及TIMP-1高表达的主要原因.

Expressions of MMP-9 and TIMP-1 after focal cerebral ischemia-reperfusion in rats

Objective To explore the expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) after focal cerebral ischemia-repeffusion injury in rats. Methods Totally 40 Wistar rats were randomly divided into 2 groups: sham-operated group and iscbemia-reperfusion group. A middle cerebral artery occlusion model was constructed in the 25 rats with Longa's method. The expressions of MMP-9 and TIMP-1 were investigated with immunohistochemistry and HE staining at 6, 24, 48, 72 h and 7 d of reperfusion following 2 h ischemia. Results MMP-9 began to be expressed at 6 h reperfusion, and was obviously increased at 24 h and reached the peak level at 48 h, and then, the expression of MMP-9 began to decrease at 72 h to a low level at 7 d. TIMP-1 positive cells began to arise at 6 h reperfusion, peaked at 24 h, decreased at 48 h and remained a low level at 7 d. The expressions of MMP-9 and TIMP-1 were mainly located in vascular endothelial cells, neurons and gitter cells. The expressions of MMP-9 and TIMP-1 were negative in sham-operated group. Conclusion The expressions of MMP-9 and TIMP-1 are induced to increase by focal cerebral ischemia-reperfusion, and vascular endothelial injury may be the main cause to the high expressions of MMP-9 and TLMP-1.