摘要
目的探讨新生大鼠缺氧缺血性脑损伤(HIBD)组织中巨噬细胞移动抑制因子(MIF)、磷酸化细胞外信号调节激酶1/2(pERK1/2)和基质金属蛋白酶-9(MMP-9)的表达变化及与脑水肿的关系。方法将144只7日龄SD大鼠随机分为假手术组、缺氧缺血组、抗MIF中和抗体干预组,于缺氧缺血模型制成后1 h、6 h、12 h、24 h、3d、7 d处死,用免疫组化方法检测脑缺血侧皮质区MIF、MMP-9的表达,Western blot法检测pERK1/2蛋白相对表达量,干湿法测定脑含水量。结果与假手术组相比,缺氧缺血组MIF在缺氧缺血后1 h表达增加,24 h达高峰(P<0.05);MMP-9在缺氧缺血后6 h表达增加,24 h达高峰(P<0.05);pERK1/2在缺氧缺血后1 h表达迅速升高,6 h迅速降低,12 h又开始增加,24 h达第2次高峰(P<0.05);脑含水量在缺氧缺血后6 h开始增加,3 d达高峰(P<0.05)。抗MIF中和抗体干预组MIF、pERK1/2、MMP-9表达及脑含水量较缺氧缺血组均下降(P<0.05)。结论缺氧缺血新生大鼠脑组织MIF表达升高,可能通过激活ERK1/2途径诱导MMP-9表达升高,进而引起脑水肿的发生。
Objective To explore the expression of macrophage migration inhibitory factor（MIF）,phosphorylated extracellular signal regulated kinases 1/2（pERK1/2）,matrix metalloproteinase-9（MMP-9） in brain and the correlations with cerebral edema after hypoxia-ischemia brain damage（HIBD）.Methods 144 seven-day-old SD rats were randomly dividend into three groups that was the sham operation group,HIBD group and intervention group with anti-MIF.Each group were executed in 1 h,6 h,12 h and 24 h,3 d,and 7 d.The expression of MIF,MMP-9 protein in the right cerebral cortex was detected with immunohistochemistry methods,the relative content of pERK1/2 was detected with Western blot and the water content of brain was evaluated with dry-wet method.Results Comparing with the sham group the expression of MIF in the HIBD group began to increase on 1 h,and peaked on 24 h（P〈0.05）,and MMP-9 began to express on 6 h,and also peaked on 24 h（P〈0.05）,while pERK1/2 expressed rapidly to peak on 1 h,and quickly decreased on 6 h,and began to increase on 12 h and reached the peak again on 24 h（P〈0.05）.Being treated with hypoxia-ischemia,the water content of brain began to increase on 6 h and peaked on 3 d（P〈0.05）.And comparing with HIBD group,the expressions of MIF,pERK1/2,MMP-9 and the water contents were decreased obviously in the anti-MIF group（P〈0.05）.ConclusionThe increased expression of MIF in the neonatal rats with hypoxia-ischemia brain damage maybe via activing the ERK1/2 ways to induce MMP-9 expressand leading to cerebral edema.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2011年第2期199-203,共5页
Journal of Sichuan University(Medical Sciences)
关键词
巨噬细胞移动抑制因子
细胞外信号调节激酶1/2
基质金属蛋白酶-9
脑水肿
缺氧缺血性脑损伤
Macrophage migration inhibitory factor Phosphorylated extracellular signal regulated kinases 1/2 Matrix metalloproteinase-9 Brain edema Hypoxia-ischemia brain damage
