坎德萨坦通过调节高血压相关的神经炎症因子来缓解外科期神经认知障碍
Zhenyu Wu1,2, Yuqing Li3, Taowu Gong4
1Department of Anesthesiology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China.
Neurochemical research
|July 29, 2025
概括
高血压增加了外科手术期间神经认知障碍 (PND) 的风险. 药物candesartan通过减少神经炎症和向特定基因,改善了PND小鼠模型中的认知功能.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 遗传学 遗传学是一种遗传学.
背景情况:
- 外科手术期间的神经认知障碍 (PND) 与神经炎症有关,这种情况也与高血压有关.
- 高血压和PND之间的因果关系,以及潜在的治疗点,仍未得到充分研究.
研究的目的:
- 调查高血压是否是PND的危险因素.
- 确定与高血压和PND相关的神经炎症点.
- 通过调节这些目标,确定一种血管激素受体阻断剂 (ARB) 甘地沙坦能否通过调节这些目标来改善PND小鼠模型中的认知功能.
主要方法:
- 门德尔随机化 (MR) 分析以评估高血压作为认知功能障碍的危险因素.
- 生物信息学和机器学习用于识别神经炎症生物标志物 (Bdkrb1,Ccr1,Thbs1).
- 使用PND小鼠模型进行体内研究,评估德沙坦治疗后的认知功能和海马体的分子变化 (RT-qPCR,西部斑点,ELISA).
主要成果:
- 核磁共振分析证实高血压是认知功能障碍的危险因素 (OR=1.0767,P=0.0057).
- Bdkrb1,Ccr1和Thbs1被确定为与高血压相关的PND的关键生物标志物.
- 康德沙坦治疗改善了PND小鼠的认知功能,减少了神经炎症 (降低IL-1β,IL-6,TNF-α,微质激活),并调节了海马中的向基因表达.
结论:
- 高血压是PND的一个重要风险因素.
- 坎德沙坦通过调节Bdkrb1,Ccr1和Thbs1.1来减轻神经炎症和改善认知功能,证明了PND的治疗潜力.
- 用坎德沙坦等ARB向海马免疫反应,可能为管理PND提供一种新的策略.
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