The roles of MMP-9/TIMP-1 in cerebral edema following experimental acute cerebral infarction in rats
The roles of MMP-9/TIMP-1 in cerebral edema following experimental acute cerebral infarction in rats
复制标题
DOI：
10.1016/j.neulet.2013.06.034
复制
发表时间：
2013-08-29
影响因子：
2.5
通讯作者：
Wang, Jun-Feng
中科院分区：
文献类型：
--
作者：
Li, Dan-Dong;Song, Jin-Ning;Wang, Jun-Feng
基质金属蛋白酶9 （MMP-9）及其内源性抑制剂组织金属蛋白酶1 （TIMP-1）调节细胞外基质（ECM）的稳态和周转。它们在急性脑梗死（ACI）中起重要作用。MMP-9和TIMP-1在ACI早期的作用尚不完全清楚。本研究探讨大鼠急性脑损伤后MMP-9和TIMP-1的时间变化及其与水肿的关系。ELISA检测血清MMP-9和TIMP-1蛋白浓度，real-time PCR检测mRNA水平。采集脑标本，测定脑含水量（BWC）。结果表明，MMP-9浓度在ACI后12 h内升高较快，12 h后升高较慢。MMP-9蛋白浓度升高早于mRNA水平升高。BWC从ACI后6 h开始升高，12 h达到峰值，72 h降至正常水平。MMP-9蛋白及其mRNA与BWC呈正相关，而TIMP-1与BWC无相关性。MMP-9/TIMP-1蛋白比MMP-9浓度与BWC的关系更为密切。这些结果表明，ACI诱导的脑水肿与血清中MMP-9水平和MMP-9/TIMP-1比值升高有关。2013爱思唯尔爱尔兰有限公司版权所有。
Matrix metalloproteinases 9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1), regulate homeostasis and turnover of the extra cellular matrix (ECM). They play important roles in acute cerebral infarction (ACI). The contributions of MMP-9 and TIMP-1 to the early stages of ACI are not completely understood. This study investigates the time course of MMP-9 and TIMP-1 and their relations to edema after ACI in rats. Serum concentrations of MMP-9 and TIMP-1 protein were measured using ELISA and mRNA level were measured using real-time PCR. Brain samples were harvested and the brain water content (BWC) was measured. Results revealed that MMP-9 concentration increased fast during the first 12 h after ACI, while after 12 h the increase was much slower. The MMP-9 protein concentration was elevated earlier than the mRNA level. BWC increased starting at 6 h after ACI to reach a peak at 12 h and decreased back to normal levels at 72 h. Both the MMP-9 protein and its mRNA were positively correlated with BWC, however no correlation was found between TIMP-1 levels and BWC. The MMP-9/TIMP-1 protein ratio was more closely correlated with BWC than the MMP-9 concentration. These results indicate that brain edema induced by ACI is associated with increased MMP-9 levels and MMP-9/TIMP-1 ratio in serum. (c) 2013 Elsevier Ireland Ltd. All rights reserved.