巨噬细胞移动抑制因子在新生大鼠缺氧缺血性脑损伤组织中的表达及作用  

Study on the Expression and the Role of Macrophage Migration Inhibitory Factor in the Brain of Neonatal Rats with Hypoxia-ischemia Brain Damage

作　　者：王丽丽[1] 郭文俊[1] 熊英[1] 杜维纳[1] 

机构地区：[1]四川大学华西第二医院新生儿科,成都610041

出　　处：《四川大学学报（医学版）》2011年第2期199-203,共5页Journal of Sichuan University(Medical Sciences)

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.

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 

分 类 号：R722.1[医药卫生—儿科]