Ac-YVAD-CMK Decreases Blood-Brain Barrier Degradation by Inhibiting Caspase-1 Activation of Interleukin-1β in Intracerebral Hemorrhage Mouse Model.
Ac-YVAD-CMK Decreases Blood-Brain Barrier Degradation by Inhibiting Caspase-1 Activation of Interleukin-1β in Intracerebral Hemorrhage Mouse Model.
复制标题
DOI：
10.1007/s12975-009-0002-z
复制
发表时间：
2010-03-01
影响因子：
6.9
通讯作者：
Tang J
中科院分区：
文献类型：
--
作者：
Wu B;Ma Q;Khatibi N;Chen W;Sozen T;Cheng O;Tang J
在众多的促炎细胞因子中，白介素1β(IL-1β)被认为是神经元损伤的关键介质。然而，为了被激活，它必须被caspase-1酶处理和切割。在这项研究中，我们测试了已知的选择性caspase-1抑制剂Ac-YVAD-CMK在小鼠脑出血(ICH)模型中的神经保护作用。66只成年雄性CD-1小鼠造成胶原酶诱导的脑出血。脑出血造模前20min左侧脑室注射AC-YVAD-CMK或赋形剂。分别于术后24小时和72小时进行脑水肿和神经功能评定。用免疫印迹法检测IL-1β、磷酸化JNK、紧密连接蛋白闭塞带1(ZO-1)和基质金属蛋白酶-9(MMP9)的表达，同时用酶谱法检测MMP9的活性。脑出血后24小时，Ac-YVAD-CMK治疗可明显减轻脑水肿，改善神经功能。其神经保护作用与下调IL-1β、JNK、MMP9及抑制ZO-1降解有关。结论：Ac-YVAD-CMK对脑出血所致脑损伤有保护作用，其神经保护作用可能与抗炎诱导的血脑屏障保护作用有关。
Among many proinflammatory cytokines, interleukin-1β (IL-1β) is considered a key mediator of neuronal injury. However, in order to become activated, it must be processed and cleaved by a caspase-1 enzyme. In this study, we tested the neuroprotective effect of Ac-YVAD-CMK, a known selective caspase-1 inhibitor, in a mouse model of intracerebral hemorrhage (ICH). Sixty-six adult male CD-1 mice were subjected to collagenase-induced ICH. Ac-YVAD-CMK or vehicle was administered into the left lateral ventricle 20 min before ICH modeling. Brain edema and neurological functions were assessed at 24 and 72 h after the surgery. Expression of IL-1β, phosphorylated JNK, tight junction protein zona occludens 1 (ZO-1), and matrix metalloproteinase-9 (MMP-9) were measured by Western blot along with MMP-9 activity measured by zymography at 24 h after ICH. At 24 h after ICH, Ac-YVAD-CMK treatment significantly reduced brain edema and improved neurological functions. The neuroprotection was associated with downregulation of IL-1β, JNK, MMP-9, and an inhibition of ZO-1 degradation in brain. We conclude that Ac-YVAD-CMK protects the brain against ICH-induced injury, and the neuroprotective effect may result from anti-inflammation-induced blood–brain barrier protection.
登录
查看更多内容
影响因子：
4.1
作者：
Masada, T;Hua, Y;Keep, RF
通讯作者：
Keep, RF
影响因子：
2.5
作者：
Lo, Wendy;Bravo, Thomas;Tang, Jiping
通讯作者：
Tang, Jiping
影响因子：
3.3
作者：
Rincon, Fred;Mayer, Stephan A
通讯作者：
Mayer, Stephan A
影响因子：
8.3
作者：
Hua, Y;Schallert, T;Xi, GH
通讯作者：
Xi, GH
影响因子：
6.3
作者：
Doyle, Kristian P.;Yang, Tao;Stenzel-Poore, Mary P.
通讯作者：
Stenzel-Poore, Mary P.