Irradiation alters MMP-2/TIMP-2 system and collagen type IV degradation in brain.
Irradiation alters MMP-2/TIMP-2 system and collagen type IV degradation in brain.
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DOI：
10.1016/j.ijrobp.2010.12.032
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发表时间：
2012-04-01
影响因子：
7
通讯作者：
Lee, Yong Woo
中科院分区：
文献类型：
--
作者：
Lee, Won Hee;Warrington, Junie P.;Sonntag, William E.;Lee, Yong Woo
关键词：
血脑屏障(BBB)破坏是辐射致中枢神经系统正常组织损伤的主要后果之一。在本研究中，我们研究了全脑照射对脑内基质金属蛋白酶(MMPs)/金属蛋白酶组织抑制物(TIMPs)和细胞外基质(ECM)降解的影响。动物接受全脑照射(单次剂量10Gyγ射线或分次剂量共40Gyγ射线)或假照射，照射后分别维持4、8、24 h。用实时定量逆转录-聚合酶链式反应(RT-PCR)检测脑组织中MMPs和TIMPs的mRNA表达水平。用原位酶谱检测MMPs的功能活性，用IV型胶原免疫荧光染色观察ECM的降解情况。与假照射对照组相比，照射组大鼠脑内基质金属蛋白酶-2、基质金属蛋白酶-9和基质金属蛋白酶组织抑制因子-1的mRNA表达水平显著升高。原位酶谱显示照射后24 h脑组织有较强的明胶溶解活性，抗基质金属蛋白酶-2抗体的存在可明显减弱照射引起的明胶溶解活性增强。照射后24小时，脑内IV型胶原免疫反应性也显著降低。而照射后4h和8h，IV型胶原水平与假照射对照组相比无明显变化。本研究首次证实了辐射可导致脑组织中基质金属蛋白酶-2和基质金属蛋白酶-2水平的失衡，提示血脑屏障基底膜的主要细胞外基质成分IV型胶原的降解可能在脑损伤的发病机制中起一定作用。
Blood-brain barrier (BBB) disruption is one of major consequences of radiation-induced normal tissue injury in the central nervous system. In the present study, we examined the effects of whole brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Animals received either whole brain irradiation (a single dose of 10 Gy γ-rays or a fractionated dose of 40 Gy γ-rays total) or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The functional activity of MMPs was measured by in situ zymography and degradation of ECM was visualized by collagen type IV immunofluorescence staining. A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h post-irradiation and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.
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辐照引起大鼠脑促炎环境的区域特异性改变。
影响因子：
2.6
作者：
Lee, Won Hee;Sonntag, William E.;Mitschelen, Matthew;Yan, Han;Lee, Yong Woo
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
8.3
作者：
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通讯作者：
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