Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats
Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats
复制标题
Ac-YVAD-cmk 通过抑制 caspase-1 介导的脑出血大鼠炎症反应改善神经功能
DOI：
10.1016/j.intimp.2019.105771
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发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Wang, Fan
中科院分区：
文献类型：
--
作者：
Liang, Hongsheng;Sun, Yong;Wang, Fan
目的：脑出血（Intracerebral hemorrhage，ICH）是一个严重的临床问题，目前缺乏有效的治疗手段.在脑出血的发展过程中，存在caspase-1介导的炎症反应。因此，本研究旨在探讨caspase-1抑制剂Ac-YVAD-cmk对脑出血的影响。材料与方法：分离小胶质细胞，凝血酶活化24 h。采用RT-PCR和Western blotting检测NLRP 3和炎症因子的转录和蛋白表达。此外，将Ac-YVAD-cmk注射到ICH模型中。ICH后24 h检测mNSS和脑含水量。结果：Ac-YVAD-cmk可抑制脑出血后24 h小胶质细胞活化，减少炎症相关因子的表达，抑制caspase-1的活化，减轻脑水肿。Ac-YVAD-cmk可减少脑出血大鼠血肿周围成熟IL-1 β/IL-18的释放，改善脑出血大鼠的行为学表现，减轻血肿周围小胶质细胞的数量。Ac-YVAD-cmk给药有可能成为ICH的一种新的治疗策略。
Objective: Intracerebral hemorrhage (ICH) is acknowledged as a serious clinical problem lacking effective treatments. And caspase-l-mediated inflammatory response happened during the progression of ICH. Therefore, we aimed to investigate the effects of caspase-1 inhibitor Ac-YVAD-cmk on ICH.Materials and methods: Microglia cells were isolated and activated by thrombin for 24 h. Then the transcript and protein expressions of NLRP3 and inflammatory factors were assessed by RT-PCR and western blotting. Moreover, Ac-YVAD-cmk was injected into the ICH model. The mNSS and brain water content were tested at 24 h post-ICH. Finally, the pathological changes of microglia activation following ICH were discovered by the immunohistochemical and HE staining ways.Results: Ac-YVAD-cmk inhibited the activation of pro-caspase-1 and decreased brain edema, in association with decreasing activated microglia and the expression of inflammation-related factors at 24 h post-ICH. Consequently, Ac-YVAD-cmk reduced the release of mature IL-1 beta/IL-18 in perihematoma, improved the behavioral performance, and alleviated microglia in perihematoma region in ICH rats.Conclusions: These results indicate that caspase-1 could amplify the plural inflammatory responses in the ICH. Administration of Ac-YVAD-cmk has the potential to be a novel therapeutic strategy for ICH.