Maresin1 alleviates neuroinflammation by inhibiting caspase-3/ GSDME-mediated pyroptosis in mice cerebral ischemia-reperfusion model

作者全名：Zhao, Maoji; Xian, Wenjing; Liu, Wenyi; Chen, Daiyu; Wang, Siqi; Cao, Jun

作者地址：[Zhao, Maoji; Xian, Wenjing; Liu, Wenyi; Chen, Daiyu; Wang, Siqi; Cao, Jun] Chongqing Med Univ, Affiliated Hosp 1, Dept Anesthesiol, 1 Youyi Rd, Chongqing 400016, Peoples R China

通信作者：Cao, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Anesthesiol, 1 Youyi Rd, Chongqing 400016, Peoples R China.

来源：JOURNAL OF STROKE & CEREBROVASCULAR DISEASES

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001246281500001

JCR分区：Q3

影响因子：2

年份：2024

卷号：33

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：Cerebral ischemia-reperfusion injury; Pyroptosis; Inflammation; GSDME; Caspase-3

摘要：Objective: To explore the mechanism of Maresin1 in reducing cerebral ischemia-reperfusion injury. Materials and methods: Male C57BL/6 mice were randomly divided (n = 5 in each group), and focal middle cerebral artery occlusion (MCAO) model was used to simulate cerebral ischemia/reperfusion injury. TTC and the Longa score were used to detect the degree of neurological deficits. Western blot was used to detect the expression levels of GSDME, GSDME-N, caspase-3 and cleaved caspase-3 in cerebral ischemic penumbra tissue, and immunofluorescence was used to detect the expression levels of GSDME-N. The mRNA expression levels of GSDME and pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) were detected by RT-PCR. Results: Compared with sham group, GSDME mRNA levels in MCAO group were significantly increased at 12 h and 24 h after reperfusion, and GSDME and GSDME-N significantly increased at 6-48 h after reperfusion. Compared with sham group, the percentage of infarct size, the Longa score, the mRNA expression levels of IL-1 beta, IL-6 and TNF-alpha, and GSDME, GSDME-N, caspase-3 and cleaved caspase-3 in MCAO group was significantly increased. Then, the percentage of infarct size and the Longa score significantly decreased after MaR1 administration, the mRNA expression levels of IL-1 beta and IL-6 downregulated, and GSDME, GSDME-N, caspase-3 and cleaved caspase-3 were also reduced. After administration of Z-DEVD-FMK(ZDF), the expression of caspase-3, cleaved caspase-3 and GSDME-N was decreased, which in MCAO+MaR1+ZDF group was not statistically significant compared with MCAO+ ZDF group. Conclusion: Maresin1 alleviates cerebral ischemia/reperfusion injury by inhibiting pyroptosis mediated by caspase-3/GSDME pathway and alleviating neuroinflammation.

基金机构：National Natural Science Foundation of China [82002024]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN202000449]

基金资助正文：the National Natural Science Foundation of China (82002024) and Scientific and Technological Research Program of Chongqing Municipal Education Commission (KJQN202000449).