缺氧缺血性脑损伤新生大鼠脑组织基质金属蛋白酶的动态变化及对细胞凋亡的影响  

Dynamic changes of matrix metalloproteinases and effect on apoptosis in hypoxic-ischemic brain injury

作　　者：杨星星[1] 阴怀清[1] 

机构地区：[1]山西医科大学第一临床医学院儿科,太原030001

出　　处：《中国新生儿科杂志》2011年第4期264-267,共4页Chinese Journal of Neonatology

基　　金：太原市科技局科技兴市基金资助(0705-026)

摘　　要：目的探讨缺氧缺血性脑损伤(HIBD)新生大鼠脑组织基质金属蛋白酶(MMPs)的动态变化及其与细胞凋亡的关系。方法将72只7日龄W istar大鼠随机分为假手术组和HIBD组,后者根据处死时间分为6 h、24 h、48 h、5天和14天组,每组12只。采用免疫组化方法测定MMP-2、MMP-9和金属蛋白酶组织抑制因子-1(TIMP-1)的表达,用流式细胞术测定脑细胞凋亡率。结果 HIBD组缺氧缺血侧大脑组织MMP-2于损伤6 h增高,5天再次升高,且峰值高于6 h组,与假手术组相比,除24 h组,其余差异均有统计学意义(P<0.05);MMP-9正常情况下有一定表达,HIBD 24 h表达达高峰,后逐渐下降,与假手术组相比,除14天组,差异均有统计学意义(P<0.05);TIMP-1正常情况下与MMP-9保持动态平衡,HIBD时两者比例失衡,后期表达增加两者平衡恢复,与假手术组相比,除6 h组和14天组,差异均有统计学意义(P<0.05)。HIBD组缺氧缺血侧脑细胞凋亡率24 h轻度升高,5天达高峰,与假手术组相比,除6 h组,差异均有统计学意义(P<0.05)。结论新生大鼠HIBD后MMP-2、MMP-9和TIMP-1的表达有不同程度变化,可能参与了HIBD的发病与修复。Objective Exploration of dynamic changes of matrix metalloproteinases in newborn rat′s brain of hypoxic ischemic brain damage（HIBD） and their relationship to apoptosis.MethodsSeventy-two Wistar rats of 7 days old were randomly divided into sham operation group and hypoxic-ischemic brain damage（HIBD） group,the latter group is further divided into five subgroups based on different time points following HIBD（6 h,24 h,48 d,5 d,14 d）（n=12 in each group）.The expression of MMP-2,MMP-9 and TIMP-1 was determined by immunohistochemical method,apoptosis rate of neurons was determined by Flow cytometry.Results MMP-2 increased slightly higher in the HIBD 6 h group than sham group,the level further peaked up in HIBD 5 d group,even higher than HIBD 6 h group,and compared with sham group,differences were statistically significant（P〈0.05） except HIBD 24 h group.MMP-9 has a certain level under normal circumstances,peaked up in HIBD 24 h group then gradually decreased,compared with sham group,except HIBD 14 d group,differences were statistically significant（P〈0.05）;TIMP-1 and MMP-9 maintain a dynamic equilibrium under normal circumstances,become imbalance after injury,the increasing expression of the latter is to restore the balance.In comparison with sham group,beside HIBD 6 h and 14 d groups,differences were statistically significant（P〈0.05）.Apopsis rate slightly increased in HIBD 24 h group,peaked at HIBD 5 d group,and in comparison with sham group,differences between groups were statistically significant beside HIBD 6 h group（P〈0.05）.Conclusions The expression of MMP-2,MMP-9 and TIMP-1 have changed differently at various level,which may be participated the pathogenesis and repair process.

关 键 词：基质金属蛋白酶类 缺氧缺血 脑 大鼠 

分 类 号：R722.1[医药卫生—儿科]