Abstract：
Postoperative cognitive dysfunction (POCD), a common complication in elderly patients after surgery, seriously affects patients\' quality of life. Long-term or repeated inhalation of sevoflurane can cause neuroinflammation, which is a risk factor for POCD. However, the underlying mechanism needs to be further explored. Recent research had revealed a correlation between neurological disorders and changes in the gut microbiota. Dysfunction of the gut microbiota is involved in the occurrence and development of central nervous system diseases. Here, we found that cognitive dysfunction in aged mice induced by sevoflurane exposure (3%, 2 hours daily, for 3 days) was related to gut microbiota dysbiosis, while probiotics improved cognitive function by alleviating dysbiosis. Sevoflurane caused a significant decrease in the abundance of Akkermansia (P<0.05), while probiotics restored the abundance of Akkermansia. Compared to those in the control group, sevoflurane significantly increased the expression of NLRP3 inflammasome-associated proteins in the gut and brain in the sevoflurane-exposed group, thus causing neuroinflammation and synaptic damage, which probiotics can mitigate (con vs. sev, P < 0.01; p+sev vs. sev, P < 0.05). In conclusion, for the first time, our study revealed that dysbiosis of the gut microbiota caused by sevoflurane anesthesia contributes to the NLRP3 inflammasome-mediated neuroinflammation and cognitive dysfunction from the perspective of the gut-brain axis. Perhaps postoperative cognitive impairment in elderly patients can be alleviated or even prevented by regulating the gut microbiota. This study provides new insights and methods for the prevention and treatment of cognitive impairment induced by sevoflurane.
摘要：
术后认知功能障碍(POCD),老年患者手术后的常见并发症，严重影响患者的生活质量。长期或反复吸入七氟醚可引起神经炎症，这是POCD的风险因素。然而,潜在机制有待进一步探索。最近的研究揭示了神经系统疾病与肠道微生物群变化之间的相关性。肠道菌群功能紊乱与中枢神经系统疾病的发生、发展密切相关。这里,我们发现七氟醚暴露诱导老年小鼠的认知功能障碍(3%，每天2小时,持续3天)与肠道微生物群菌群失调有关，而益生菌通过缓解生态失调改善认知功能。七氟醚引起Akkermansia丰度显著降低(P<0.05),而益生菌恢复了大量的Akkermansia。与对照组相比，七氟醚显著增加七氟烷暴露组肠和脑中NLRP3炎性体相关蛋白的表达,从而引起神经炎症和突触损伤，哪些益生菌可以缓解(convs.sev,P<0.01;p+sevvs.sev,P<0.05)。总之,第一次,我们的研究表明,从肠-脑轴的角度来看,七氟醚麻醉引起的肠道微生物群失调有助于NLRP3炎性体介导的神经炎症和认知功能障碍.也许可以通过调节肠道菌群来减轻甚至预防老年患者术后认知功能障碍。本研究为七氟醚所致认知功能障碍的防治提供了新的思路和方法。
