缺氧缺血性脑损伤新生大鼠脑组织 MMP-9、TIM P-1表达变化及意义

摘要

目的：观察缺氧缺血性脑损伤（HIBD）新生大鼠脑组织基质金属蛋白酶9（MMP-9）、金属蛋白酶组织抑制因子1（TIMP-1）的表达变化，并探讨其意义。方法将72只新生大鼠随机分为观察组和对照组各36只，观察组建立HIBD模型，对照组分离左侧颈总动脉后不结扎，也不予低氧处理。两组分别于造模后6 h（ T0）、12 h（ T1）、24 h（ T2）、72 h（ T3）、5 d（ T4）、7 d（ T5）各处死6只，采用HE染色观察造模后72 h的脑组织病理变化，免疫组化SP法检测脑组织MMP-9、TIMP-1，计算脑组织含水量。结果观察组大脑皮质水肿明显，细胞变性、坏死，神经元细胞数目减少，炎性细胞增多；对照组脑组织细胞形态结构清晰完整，间质内未见出血、坏死及水肿。观察组脑组织MMP-9、TIMP-1表达及含水量均先升高后降低，对照组无明显变化。观察组T0～T5时点脑组织MMP-9、TIMP-1表达及含水量均高于对照组，P均＜0．05。结论 HIBD新生大鼠脑组织MMP-9和TIMP-1表达升高，二者可能与HIBD过程中血管源性脑水肿的形成有关。%Objective To observe the expression changes of matrix metalloproteinase 9 ( MMP-9) and tissue inhibitor metalloproteinase (TIMP-1) in the brain tissue of rats with hypoxic-ischemic brain damage (HIBD) and to explore its sig-nificance .Methods Seventy-two neonatal rats were randomly divided into the observation group and control group , and 36 rats in each group .HIBD model was established in the observation group .In the control group , we separated the left com-mon carotid artery of rats and did not ligature , and rats were not treated with hypoxia .After 6 h ( T0 ) , 12 h ( T1 ) , 24 h (T2) and 72 h (T3), 5 d (T4), 7 d (T5) of modeling, 6 rats of each group were killed respectively.The pathological changes in the brain tissues was observed by HE staining after modeling for 72 h, the expression of MMP-9 and TIMP-1 in the brain tissues was detected by immunohistochemical SP method , and the water content of the brain tissues was calculat-ed.Results In the observation group , cortical brain edema , degeneration and necrosis of the cells were observed , the neuronal cells were decreased and inflammatory cells were increased;while, in the control group, the morphology structure of brain tissue was clear and complete , no interstitial hemorrhage , necrosis and edema were observed .The expression of TIMP-1 and MMP-9 in the brain tissues and the water content increased first and then decreased in the observation group , and no significant change was found in the control group .At T0-T5 in the brain tissues, the expression of MMP-9, TIMP-1 and water content in the observation group were higher than those of the control group (all P<0.05).Conclusion The expression of MMP-9 and TIMP-1 increases in the brain tissues of HIBD neonatal rats , and it may be related with the for-mation of HIBD in vasogenic brain edema .