Liao Huihui, Wang Xinyi, Yang Chenyi, Wang Zixuan, Liu Xing, Liu Huan, Zhang Jingwei, Shen Huai, Wang Haiyun
The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China; Department of Anesthesiology, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China.
Nankai University, 300071 Tianjin, China; Department of Anesthesiology, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Nankai University Affinity the Third Central Hospital, Tianjin 300170, China; The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China.
Exp Neurol. 2025 Oct;392:115328. doi: 10.1016/j.expneurol.2025.115328. Epub 2025 May 31.
Surgery and anesthesia may compromise fragile brain function in the elderly, potentially precipitating cognitive decline or Alzheimer's disease (AD) following perioperative neurocognitive disorder (PND). Vasoactive intestinal peptide (VIP) exhibits anti-inflammatory properties via the gut-brain axis. Nevertheless, whether VIP regulation enhances cognitive function in the fragile brains of aged rat and the underlying mechanisms remain to be elucidated.
A model of fragile brain function was established in elderly rats through bilateral common carotid artery ligation. Cognitive impairment induced by anesthesia and surgery was evaluated using behavioral assays, quantification of cognition-related protein levels, analysis of inflammatory markers, assessment of microglial polarization, and examination of intestinal mucosal and blood-brain barrier integrity. Adeno-associated virus (AAV) was employed to upregulate VIP expression in the colon, and subsequent alterations in the aforementioned parameters were recorded.
Cognitive performance was evaluated through behavioral assays, while cognition-related protein levels were determined using Western blot analysis. Anesthesia and surgical interventions exacerbated cognitive deficits in rats with fragile brain function. VIP upregulation significantly ameliorated post-anesthesia and surgery cognitive deficits, normalized cognition-related protein expression, attenuated the inflammatory response, and promoted the repair of both intestinal mucosal and blood-brain barriers.
These findings indicate that VIP upregulation mitigates anesthesia- and surgery-induced cognitive impairment and its progression in aged rats with fragile brain function a, primarily by modulating the inflammatory response and preserving the gut and blood-brain barrier integrity. This study offers valuable insights potential preventive strategies against cognitive decline.
手术和麻醉可能会损害老年人脆弱的脑功能，在围手术期神经认知障碍（PND）后可能会促使认知能力下降或患阿尔茨海默病（AD）。血管活性肠肽（VIP）通过肠-脑轴发挥抗炎特性。然而，VIP调节是否能增强老年大鼠脆弱大脑的认知功能及其潜在机制仍有待阐明。
通过双侧颈总动脉结扎在老年大鼠中建立脆弱脑功能模型。使用行为学检测、认知相关蛋白水平定量、炎症标志物分析、小胶质细胞极化评估以及肠黏膜和血脑屏障完整性检查来评估麻醉和手术诱导的认知障碍。采用腺相关病毒（AAV）上调结肠中VIP的表达，并记录上述参数随后的变化。
通过行为学检测评估认知表现，使用蛋白质印迹分析确定认知相关蛋白水平。麻醉和手术干预加剧了脑功能脆弱大鼠的认知缺陷。VIP上调显著改善了麻醉和手术后的认知缺陷，使认知相关蛋白表达正常化，减轻了炎症反应，并促进了肠黏膜和血脑屏障的修复。
这些发现表明，VIP上调可减轻麻醉和手术诱导的老年脑功能脆弱大鼠的认知障碍及其进展，主要是通过调节炎症反应和维持肠道及血脑屏障完整性实现的。本研究为预防认知能力下降的潜在策略提供了有价值的见解。
