通过促进微质NLRP3炎症酶激活,PIM-1会加剧败血症相关的脑病变
Xiaomeng Ji1, Jingquan Dong2, Wenting Zhu1
1Institute of Neuroscience, Department of Neurosurgery, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, 222000, China; Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
Free radical biology & medicine
|October 2, 2025
概括
通过激活微质和神经炎症,PIM-1激酶驱动败血症相关脑病变 (SAE). 用urolithin B抑制PIM-1为SAE提供了一个潜在的治疗策略,改善认知功能.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 败血症相关脑病变 (SAE) 是败血症的常见并发症,导致死亡率和认知缺陷.
- 微质线粒体反应性氧物种 (mtROS) 和NLRP3炎症酶激活是SAE病变的关键驱动因素.
- 尽管已知它对mtROS和NLRP3的调节,但PIM-1激酶在SAE中的作用尚未得到充分理解.
研究的目的:
- 调查PIM-1在SAE发展中的作用.
- 探索SAE中PIM-1抑制的治疗潜力.
主要方法:
- 建立了SAE的小鼠模型,使用结和穿孔 (CLP).
- 使用了激活微质细胞 (BV-2细胞) 的体外模型,具有siRNA干扰和RNA-seq.
- 通过分子对接选乌罗立B (UB) 作为PIM-1抑制剂,并评估其 in vivo 和 in vitro 的疗效.
主要成果:
- 在SAE模型中,PIM-1被上调,与大脑损伤相关.
- 抑制PIM-1降低了微质激活和炎症性细胞因子的释放.
- 通过调节mtROS/NLRP3通路,UB的PIM-1抑制改善了SAE,减少了神经元损伤,并改善了认知障碍.
结论:
- 通过调解微质激活和神经炎症,PIM-1在SAE进展中发挥着关键作用.
- 向PIM-1,特别是用urolithin B,显示出SAE的显著治疗潜力.
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