MMP-9/TIMP-1在大鼠弥漫性脑损伤后早期的表达及意义

目的探讨基质金属蛋白酶-9及其抑制剂TIMP-1在大鼠弥漫性脑损伤后早期的表达变化与继发脑损伤的关系。方法荧光实时定量RT-PCR分别测定MMP-9mRNA和TIMP-1mRNA在大鼠弥漫性脑损伤早期不同时程的表达，干湿重法测定脑水分含量，光镜和电镜观察血脑屏障结构的变化。结果与假手术对照组相比，外伤后1?h大鼠脑组织中MMP-9mRNA开始增加，伤后12h达到高峰并持续7?d（P<0.01）；TIMP-1mRNA表达6h明显升高，24h达高峰，表达量增加1倍，并持续7d（P<0.01）。脑组织含水量比假手术对照组明显增加，光镜及电镜下可见炎性反应和毛细血管的超微结构破坏、神经元变性水肿和坏死，72h损伤最重。 结论大鼠外伤后诱导MMP-9mRNA和TIMP-1mRNA表达增加，可能参与了弥漫性脑损伤后早期脑水肿和神经元损伤的继发脑损害病理过程。

Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 after diffuse brain injury and their significance in rats

Objective To explore whether expressions of matrix metalloproteinase-9 and tissuce inhibitor of metalloproteinase-1 in early diffuse brain injured tissues have a correlation with second brain injury in rats.Methods Real-time quantitative PCR was used to determine expressions of MMP-9mRNA and TIMP-1mRNA,the dry-wet method to determine the containing water measure in the brain,and histological techniques and electron microscopy to determine the ultrastructural blood brain barrier at different time-points after diffuse brain injury in rats.Results Compared with the sham-operated group,expression of MMP-9mRNA started to increase at the first hour,peaked at the 12th hour(P<0.01) and persisted up to one week.Expression of TIMP-1mRNA also peaked at the 24th hour and persisted up to one week(P<0.01).Ultra-structures of the neurons were injured,edema and necrosis were diffuse and distinct at the 72 th hour under light microscopy and electron microscopy.Conclusions Expressions of MMP-9mRNA and TIMP-1mRNA are increased after diffuse brain injury in rats,indicating that MMP-9 and TIMP-1 are closely related to brain edema and neuronal damage in early second brain injury in rats.