ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway.
ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway.
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ACT001通过抑制促炎细胞因子的产生和JAK-STAT信号通路的表达，改善脓毒症小鼠的心血管功能。
DOI：
10.3389/fphar.2023.1265177
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
脓毒症是一种由微生物感染引起的危及生命的多器官功能障碍综合征（MODS），在世界范围内具有很高的发病率和死亡率。脓毒症诱导的心肌病（SIC）和凝血功能障碍促进了脓毒症不良结局的进展。在这里，我们报告了ACT 001，一种改良的化合物，parthenopathy，提高脓毒症小鼠的生存。本研究采用盲肠结扎穿孔（CLP）模型诱导SIC。采用经胸超声心动图和HE染色法观察ACT 001对脓毒症心功能不全的影响。我们的研究结果表明，ACT 001显着改善心脏功能，减少SIC。凝血加速脓毒症中的器官损伤。我们发现ACT 001在FeCl 3诱导的颈动脉血栓形成实验中降低了血液凝固。ACT 001还减少了中性粒细胞细胞外陷阱（NET）的产生。心脏组织的RNA测序显示，ACT 001显著下调促炎细胞因子和JAK-STAT信号通路的表达。这些结果用实时PCR和ELISA证实。总之，我们发现ACT 001通过保护心血管系统拯救了感染性休克小鼠。这部分是通过抑制促炎细胞因子的产生和下调JAK-STAT信号传导介导的。ACT 001通过抑制IL-6、STAT 3和促炎细胞因子的表达改善脓毒症小鼠的心血管功能。
Sepsis is a life-threatening multiple organ dysfunction syndrome (MODS) caused by a microbial infection that leads to high morbidity and mortality worldwide. Sepsis-induced cardiomyopathy (SIC) and coagulopathy promote the progression of adverse outcomes in sepsis. Here, we reported that ACT001, a modified compound of parthenolide, improved the survival of sepsis mice. In this work, we used cecal ligation and puncture (CLP) model to induce SIC. Transthoracic echocardiography and HE staining assays were adopted to evaluate the influence of ACT001 on sepsis-induced cardiac dysfunction. Our results showed that ACT001 significantly improved heart function and reduced SIC. Coagulation accelerates organ damage in sepsis. We found that ACT001 decreased blood clotting in the FeCl3-induced carotid artery thrombosis experiment. ACT001 also reduced the production of neutrophil extracellular traps (NETs). RNA-sequencing of heart tissues revealed that ACT001 significantly downregulated the expression of pro-inflammatory cytokines and the JAK-STAT signaling pathway. These results were confirmed with real-time PCR and ELISA. In summary, we found ACT001 rescued mice from septic shock by protecting the cardiovascular system. This was partially mediated by inhibiting pro-inflammatory cytokine production and down-regulating the JAK-STAT signaling. ACT001 improves cardiovascular function in sepsis mice by inhibiting the expression of IL-6, STAT3, and pro-inflammatory cytokines.
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影响因子：
4.6
作者：
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影响因子：
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DOI：
10.3791/54479
发表时间：
2016-09-05
期刊：
Journal of visualized experiments : JoVE
影响因子：
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