Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; Department of Anesthesiology, Women and Children's Health Care Hospital of Linyi, Linyi 276017, Shandong, China.
Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
Brain Res. 2022 Sep 15;1791:148000. doi: 10.1016/j.brainres.2022.148000. Epub 2022 Jun 30.
Sepsis is associated with multiple organ dysfunction, and the brain is particularly vulnerable. Sepsis-associated encephalopathy (SAE) increases the mortality of patients with sepsis; however, the pathogenesis of SAE remains unclear. Methane, the simplest aliphatic hydrocarbon, has been reported to have anti-inflammatory and organ-protective effects. This study aimed to investigate the effects of methane on the cognitive deficits in mice with experimental sepsis. We randomly divided C57BL/6 male mice into sham, cecal ligation and puncture (CLP), and CLP + methane-rich saline (MS) groups. Twenty-four hours after surgery, behavioral tests were conducted on surviving mice and the hippocampus were collected for biochemical analysis. We found that CLP resulted in cognitive deficits in septic mice. A physiological mechanistic investigation revealed that microglia in the hippocampus are largely activated, coupled with the production of inflammatory cytokines and reactive oxygen species (ROS). Notably, methane inhibited the activation of microglia in the hippocampus, reduced the severity of inflammation, diminished the generation of ROS, and ultimately alleviated behavioral impairment in septic mice. Together, these show that treatment with methane ameliorated cognitive deficits in septic mice, which is partly related to the anti-inflammatory and antioxidative effects in the hippocampus.
脓毒症与多器官功能障碍有关，而大脑尤其容易受到影响。脓毒症相关性脑病（SAE）会增加脓毒症患者的死亡率；然而，SAE 的发病机制仍不清楚。甲烷是最简单的脂肪烃，已被报道具有抗炎和器官保护作用。本研究旨在探讨甲烷对实验性脓毒症小鼠认知功能障碍的影响。我们将 C57BL/6 雄性小鼠随机分为假手术组、盲肠结扎穿孔（CLP）组和 CLP+富含甲烷生理盐水（MS）组。手术后 24 小时，对存活的小鼠进行行为测试，并采集海马进行生化分析。我们发现 CLP 导致脓毒症小鼠出现认知功能障碍。一项生理机制研究表明，海马中的小胶质细胞被大量激活，同时产生炎症细胞因子和活性氧（ROS）。值得注意的是，甲烷抑制了海马中小胶质细胞的激活，减轻了炎症的严重程度，减少了 ROS 的产生，最终缓解了脓毒症小鼠的行为障碍。综上所述，这些结果表明，甲烷治疗改善了脓毒症小鼠的认知功能障碍，这部分与海马中的抗炎和抗氧化作用有关。
