大鼠脑缺血再灌注后MMP-9、MMP-2表达与脑水肿的关系

A study on the expression of MMP-9,MMP-2 and the relationship between MMP-9,MMP-2 and brain edema in cerebral ischemia reperfusion rats

目的:观察大鼠脑缺血再灌注后基质金属蛋白酶9(MMP-9)、基质金属蛋白酶2(MMP-2)的动态变化规律及其与脑水肿的关系。方法:将80只SD大鼠分为假手术组(n=10)和实验组(再灌注6 h、12 h、24 h、48 h、72 h、7 d和10 d组,n=10)。线栓法复制大鼠左侧大脑中动脉缺血再灌注模型,缺血2 h,再灌注6 h、12 h、24 h、48 h、72 h、7 d和10 d测定大鼠神经功能缺损评分;断头取脑,按Elliot公式计算脑组织含水量,免疫组织化学法测定相应时间点MMP-2、MMP-9免疫阳性细胞数。结果:实验组再灌注后6 h出现神经功能障碍,48 h最严重,10 d仍未完全恢复,与假手术组比较,差异有统计学意义(P<0.05)。实验组再灌注6 h出现脑水肿,48 h最严重,7 d时脑水肿仍存在,与假手术组比较,差异有统计学意义(P<0.05)。实验组再灌注6 h有少量的MMP-9免疫阳性细胞,12 h开始增多,48 h达到高峰,与假手术组比较,差异有统计学意义(P<0.05)。实验组再灌注24 h见少量MMP-2免疫阳性细胞,48 h逐渐增多,72 h最多,7 d和10 d仍有较多表达,与假手术组比较,差异有统计学意义(P<0.05)。结论:脑缺血再灌注后MMP-2和MMP-9均升高,两者表达方式的不同,提示MMP-9主要参与脑缺血再灌注后脑水肿形成,MMP-2可能与组织修复和神经再生有关。

Objective： To observe rule the of the dynamic change of the expression of matrix metalloproteinases- 9 （MMP-9） and matrix metalloproteinases-2 （MMP-2） after cerebral ischemia reperfusion rats, and the relation- ship between the expression of MMP-9, MMP-2 and brain edema. Methods： Eighty SD rats were randomly divided into control group （n=10） and experiment group （reperfusion for 6 h, 12 h, 48 h, 72 h, 7 d and 10 d groups, n=10）. The model of focal brain ischemia reperfusion was made by occluding the middle cerebral artery （MCA） for 2 h and reperfusion for 6 h, 12 h, 48 h, 72 h, 7 d and 10 d. The score of neurological deficits was determined at the time points. At each time point, the water content of rats brain were measured with Elliot formula and the expression of MMP-9 and MMP-2 was examined with the immunohistochemical staining. Results： Nerve func- tional disorder appeared at 6 h. The score of neurological deficits peaked at 48 h, didn＇t reach normal at 10 d, there was statistically significance compared to the sham-operation group （P〈 0.05）. The water of brain content increased at 6 h, and peaked at 48 h, existed in 7 d, there was statistically significance compared to the sham- operation group （P〈0.05）. The amount of MMP-9 positive cells were observed at 6 h, increased at 12 h, and peaked at 48 h, there was statistically significance compared to the sham-operation group （P〈0.05）. The amount of MMP-2 positive cells were observed at 24 h, increased at 48 h, and peaked at 72 h, then decreased gradually in 7 d and 10 d, there was statistically significance compared to the sham-operation group （P〈0. 05）. Conclusion： The amounts of MMP-9 and MMP-2 positive cells increase after cerebral ischemia reperfusion, the different expression patterns of MMP-2 and MMP-9 suggest that MMP-9 mainly participates in the formation of brain edema, MMP-2 may 10articipate in reoairation of injure and regeneration of nerve.