JNK-IN-8 治疗通过抑制 JNK/NF-κB 介导的 NLRP3 炎症小体改善 ARDS 诱导的认知障碍。
JNK-IN-8 treatment improves ARDS-induced cognitive impairment by inhibiting JNK/NF-κB-mediated NLRP3 inflammasome.
机构信息
Department of Intensive Care Unit, The First Hospital of Jiaxing & First Affiliated Hospital of Jiaxing University, Jiaxing, China.
Department of Pathology, The First Hospital of Jiaxing & First Affiliated Hospital of Jiaxing University, Jiaxing, China.
出版信息
Brain Behav. 2023 May;13(5):e2980. doi: 10.1002/brb3.2980. Epub 2023 Mar 29.
PURPOSE
Cognitive impairment is a critical complication of acute respiratory distress syndrome (ARDS). However, effective interventions are lacking. Growing evidence demonstrates that c-Jun N-terminal kinase (JNK)-mediated neuroinflammation is involved in the development of ARDS. Therefore, we hypothesized that the JNK pathway is involved in ARDS-induced cognitive impairment.
METHODS
An in vivo rat model of ARDS was established by treating it with lipopolysaccharide. The cognitive function was assessed by behavioral tests. The levels of pro-inflammatory cytokines, JNK and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) were analyzed by enzyme-linked immunosorbent assay, western blot, or immunohistochemical analysis.
RESULTS
We found that JNK inhibitor 8 (JNK-IN-8) alleviated cognitive impairment, neuroinflammation, and NLRP3 inflammasome activation in the ARDS rat model. Additionally, an in vivo study showed that the protective effect of JNK-IN-8 on cognitive impairment was blocked by nigericin, an NLRP3 activator.
CONCLUSIONS
Our data suggest that JNK-IN-8 treatment improves ARDS-induced cognitive impairment by inhibiting the JNK/nuclear factor-κB-mediated NLRP3 inflammasome.
目的
认知障碍是急性呼吸窘迫综合征（ARDS）的严重并发症。然而，目前缺乏有效的干预措施。越来越多的证据表明，c-Jun N 末端激酶（JNK）介导的神经炎症参与了 ARDS 的发生发展。因此，我们假设 JNK 通路参与了 ARDS 引起的认知障碍。
方法
通过给予脂多糖建立 ARDS 大鼠模型，通过行为测试评估认知功能。采用酶联免疫吸附试验、Western blot 或免疫组织化学分析检测促炎细胞因子、JNK 和 NOD、LRR 和 pyrin 结构域包含蛋白 3（NLRP3）的水平。
结果
我们发现 JNK 抑制剂 8（JNK-IN-8）减轻了 ARDS 大鼠模型中的认知障碍、神经炎症和 NLRP3 炎性小体激活。此外，一项体内研究表明，NLRP3 激活剂 Nigericin 阻断了 JNK-IN-8 对认知障碍的保护作用。
结论
我们的数据表明，JNK-IN-8 通过抑制 JNK/核因子-κB 介导的 NLRP3 炎性小体来改善 ARDS 引起的认知障碍。
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