局部亚低温干预对实验大鼠脑出血后MMP-2/9表达及脑水肿的影响  

The effect of local mild hypothermia on MMP-2/9 expression and brain edema in experimental intracerebral hemorrhage in rats

作　　者：张建平[1] 孟凡超[2] 代吉文[2] 张新颜[1] 

机构地区：[1]河南省商丘市第一人民医院神经内科,商丘476100 [2]郑州大学第二附属医院神经内科

出　　处：《中华物理医学与康复杂志》2007年第10期649-652,共4页Chinese Journal of Physical Medicine and Rehabilitation

摘　　要：目的探讨局部亚低温干预对大鼠自体血注入法脑出血模型基质金属蛋白酶-2/9(MMP-2/ 9)表达及脑水肿的影响。方法将165只Wistar大鼠随机分为常温假手术组(15只)、常温实验组(75只)及亚低温实验组(75只)。亚低温实验组于脑内注血后给予持续4h的局部亚低温治疗。各组大鼠分别于术后6h,24h,72h,5d及7d时进行脑组织水含量、血脑屏障(BBB)通透性测定,并同时应用免疫组化法测定脑组织MMP-2/9表达水平。结果常温实验组大鼠脑组织水含量、BBB通透性及MMP-9表达水平均于术后6h时开始增高,于72h时达到高峰,至术后7d时仍明显高于常温假手术组;MMP-2在术后24h才开始有少量表达,于术后5d时达到高峰,至7d时仍保持较高表达水平。亚低温实验组大鼠脑组织水含量、BBB通透性及MMP-2/9的表达情况均与常温实验组接近,但其各项指标数据均较常温实验组明显降低。常温实验组和亚低温实验组大鼠MMP-9的表达与脑组织水含量及BBB通透性的变化均呈正相关,而MMP-2的表达与二者变化均无明显相关性。结论亚低温干预可能具有抑制脑出血后MMP-2/9表达的作用,从而保护BBB,减轻脑水肿及炎症反应。Objective To study the effect of local mild hypothermia on the expression of matrix metalloproteinases-2/9 （MMP-2/9） and brain edema in experimental intracerebral hemorrhage （ICH） in rat. Methods One hundred and forty-five Wistar rats were randomly divided into a normothermia sham-operation （NSO） group （n = 15） , a normothermia intracerebral hemorrhage （NICH） group （ n = 75 ） and a mild hypothermia intracerebral hemorrhage （MHICH） group （ n = 75 ）. Autologous arterial blood was stereotaxically injected into the right caudate nucleus of the rats of the NICH and MHICH groups to make intracerebral hemorrhage model. The rats in the MHICH group were then subjected to 4 hours of local mild hypothermia, while those in the NICH group were under the room temperature. The brain water content, permeability of brain-blood barrier （BBB） and expressions of MMP-2/9 were measured by immunohistochemistry method at 6 h, 24 h, 72 h, 5 d and 7 d after operation. Results In NICH group, the brain water content, permeability of BBB and expression of MMP-9 all began to increase at 6 h and peaked at 3 d after injection of blood and still higher than the NSO group at 7 d. The expression of MMP-2 only began to increase little at 24 h and peaked at 5 d after operation and remained highly expressed at 7 d. In the MHICH group, the changes of brain water content, permeability of BBB and expression of MMP-9 were similar to those of the NICH group, but the extent of changes was significantly lower at the every time point. In NICH group and MHICH group, MMP-9 expression was positively correlated with both the brain water content and the permeability of BBB, but MMP-2 expression was not correlated with them. Conclusion Mild hypothermia might protect BBB against injury caused by ICH and relieve brain edema and inflammation reaction through inhibiting the expression of MMP-2/9.

关 键 词：亚低温 基质金属蛋白酶 脑出血 脑水肿 

分 类 号：R743.34[医药卫生—神经病学与精神病学]