Yang Ning, Li Lunxu, Li Zhengqian, Ni Cheng, Cao Yiyun, Liu Taotao, Tian Miao, Chui Dehua, Guo Xiangyang
Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.
Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
Neurosci Lett. 2017 May 10;649:85-92. doi: 10.1016/j.neulet.2017.04.019. Epub 2017 Apr 12.
Post-operative cognitive dysfunction (POCD) is a commonly seen postoperative complication in elderly patients and its underlying mechanisms are still unclear. Autophagy, a degradation mechanism of cellular components, is required for cell survival and many physiological processes. Although propofol is one of the most commonly used intravenous anesthetics, investigations into its mechanisms and effects on cognition in aged rodents are relatively scarce. In this study, we evaluate the influence of propofol on learning and memory, and identify the potential role of hippocampal autophagy in propofol-induced cognitive alterations in aged rats. The results demonstrate that 4h propofol exposure significantly impaired cognitive performance through the inhibition of hippocampal autophagy. Diaminodiphenyl sulfone (dapsone, DDS), which was used as an anti-leprosy drug, has been found to have neuroprotective effects. We have previously demonstrated that DDS can improve surgical stress induced depression- and anxiety-like behavior. We therefore aimed to investigate the effects of DDS on propofol-induced cognitive dysfunction and associated hippocampal autophagy responses. Pretreatment with 5mg/kg or 10mg/kg body weight DDS significantly improved the behavioral disorder and upregulated the inhibited autophagic response in aged rats. Our exploration is the first to establish an in vivo link between central autophagy and cognitive dysfunction in aged hippocampus after propofol anesthesia and demonstrate that the prophylactic effect of DDS on the cognitive impairment induced by propofol involves autophagy. These findings may imply a potential novel target for the treatment in patients with propofol anesthesia-induced cognitive impairment.
术后认知功能障碍（POCD）是老年患者常见的术后并发症，其潜在机制尚不清楚。自噬是细胞成分的一种降解机制，是细胞存活和许多生理过程所必需的。尽管丙泊酚是最常用的静脉麻醉药之一，但对其在老年啮齿动物中的作用机制和对认知的影响的研究相对较少。在本研究中，我们评估了丙泊酚对学习和记忆的影响，并确定海马自噬在丙泊酚诱导的老年大鼠认知改变中的潜在作用。结果表明，4小时丙泊酚暴露通过抑制海马自噬显著损害认知能力。氨苯砜（DDS）作为一种抗麻风病药物，已被发现具有神经保护作用。我们之前已经证明DDS可以改善手术应激诱导的抑郁和焦虑样行为。因此，我们旨在研究DDS对丙泊酚诱导的认知功能障碍和相关海马自噬反应的影响。以5mg/kg或10mg/kg体重的DDS预处理可显著改善老年大鼠的行为障碍，并上调被抑制的自噬反应。我们的探索首次在丙泊酚麻醉后老年海马的中枢自噬与认知功能障碍之间建立了体内联系，并证明DDS对丙泊酚诱导的认知损伤的预防作用涉及自噬。这些发现可能意味着为丙泊酚麻醉诱导的认知损伤患者的治疗提供了一个潜在的新靶点。
