布皮瓦卡因通过抑制YES1介导的YAP1酸化来加剧术后认知功能障碍
1Department of Anesthesiology, Huai'an Hospital of Traditional Chinese Medicine, No. 3, Heping Road, Qingjiangpu District, Huai'an, 223001, Jiangsu, People's Republic of China.
Experimental brain research
|October 28, 2025
概括
布皮瓦卡因通过降低YES原基因1 (YES1) 和YAP1酸化而导致术后认知功能障碍 (POCD),导致DNA损伤. 恢复YES1可能会扭转这些影响,为POCD提供潜在的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 布皮瓦卡因 (Bupivacaine) 是人类和马类医学中广泛使用的局部麻醉剂.
- 手术后认知功能障碍 (POCD) 是麻醉和手术后的一个令人担忧的并发症.
- 在布皮瓦卡因诱导的POCD背后的精确分子机制仍然不完全理解.
研究的目的:
- 阐明布皮瓦卡因诱导的术后认知功能障碍 (POCD) 的分子机制.
- 调查YES原瘤基因1 (YES1) 和YES相关蛋白1 (YAP1) 在布皮瓦卡因诱导的POCD中信号传递的作用.
- 评估针对YES1/YAP1信号的治疗潜力.
主要方法:
- 使用布皮瓦卡因和手术开发POCD小鼠模型.
- 使用行为测试评估认知功能 (莫里斯水迷宫,开放场地测试,新型物体识别).
- 在体内和体外模型 (SH-SY5Y细胞) 中分析神经元DNA损伤和分子信号通路 (YES1,YAP1酸化).
- 使用YAP1抑制剂维特波芬的药理干预.
主要成果:
- 布皮瓦卡因的使用损害了小鼠的认知功能,通过增加逃跑延迟,减少平台穿越,减少运动和较低的歧视指数来证明这一点.
- 这些认知缺陷与抑制YES1表达和降低海马组织中YAP1酸化有关.
- 通过增强YAP1酸化,YES1过度表达改善了布皮瓦卡因诱导的POCD和神经元DNA损伤.
- 甲治疗逆转了YES1过度表达的保护作用,并加剧了POCD和DNA损伤.
结论:
- 布皮瓦卡因通过抑制YES1表达和随后的YAP1酸化来诱导POCD,从而导致神经元DNA损伤.
- 针对YES1/YAP1通路代表了一种有前途的治疗策略,用于缓解布皮瓦卡因引起的认知障碍.
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