PDF(Pubmed)
Abstract：
UNASSIGNED: Sepsis is recognized as a multiorgan and systemic damage caused by dysregulated host response to infection. Its acute systemic inflammatory response highly resembles that of lipopolysaccharide (LPS)-induced endotoxemia. Propofol and dexmedetomidine are two commonly used sedatives for mechanical ventilation in critically ill patients and have been reported to alleviate cognitive impairment in many diseases. In this study, we aimed to explore and compare the effects of propofol and dexmedetomidine on the encephalopathy induced by endotoxemia and to investigate whether ferroptosis is involved, finally providing experimental evidence for multi-drug combination in septic sedation.
UNASSIGNED: A total of 218 C57BL/6J male mice (20-25 g, 6-8 weeks) were used. Morris water maze (MWM) tests were performed to evaluate whether propofol and dexmedetomidine attenuated LPS-induced cognitive deficits. Brain injury was evaluated using Nissl and Fluoro-Jade C (FJC) staining. Neuroinflammation was assessed by dihydroethidium (DHE) and DCFH-DA staining and by measuring the levels of three cytokines. The number of Iba1+ and GFAP+ cells was used to detect the activation of microglia and astrocytes. To explore the involvement of ferroptosis, the levels of ptgs2 and chac1; the content of iron, malondialdehyde (MDA), and glutathione (GSH); and the expression of ferroptosis-related proteins were investigated.
UNASSIGNED: The single use of propofol and dexmedetomidine mitigated LPS-induced cognitive impairment, while the combination showed poor performance. In alleviating endotoxemic neural loss and degeneration, the united sedative group exhibited the most potent capability. Both propofol and dexmedetomidine inhibited neuroinflammation, while propofol\'s effect was slightly weaker. All sedative groups reduced the neural apoptosis, inhibited the activation of microglia and astrocytes, and relieved neurologic ferroptosis. The combined group was most prominent in combating genetic and biochemical alterations of ferroptosis. Fpn1 may be at the core of endotoxemia-related ferroptosis activation.
UNASSIGNED: A total of 218 C57BL/6J male mice (20-25 g, 6-8 weeks) were used. Morris water maze (MWM) tests were performed to evaluate whether propofol and dexmedetomidine attenuated LPS-induced cognitive deficits. Brain injury was evaluated using Nissl and Fluoro-Jade C (FJC) staining. Neuroinflammation was assessed by dihydroethidium (DHE) and DCFH-DA staining and by measuring the levels of three cytokines. The number of Iba1+ and GFAP+ cells was used to detect the activation of microglia and astrocytes. To explore the involvement of ferroptosis, the levels of ptgs2 and chac1; the content of iron, malondialdehyde (MDA), and glutathione (GSH); and the expression of ferroptosis-related proteins were investigated.
UNASSIGNED: The single use of propofol and dexmedetomidine mitigated LPS-induced cognitive impairment, while the combination showed poor performance. In alleviating endotoxemic neural loss and degeneration, the united sedative group exhibited the most potent capability. Both propofol and dexmedetomidine inhibited neuroinflammation, while propofol\'s effect was slightly weaker. All sedative groups reduced the neural apoptosis, inhibited the activation of microglia and astrocytes, and relieved neurologic ferroptosis. The combined group was most prominent in combating genetic and biochemical alterations of ferroptosis. Fpn1 may be at the core of endotoxemia-related ferroptosis activation.
摘要：
■脓毒症被认为是由宿主对感染的反应失调引起的多器官和全身性损害。其急性全身性炎症反应与脂多糖（LPS）诱导的内毒素血症非常相似。丙泊酚和右美托咪定是危重病人机械通气常用的两种镇静剂，已被报道可缓解多种疾病的认知障碍。在这项研究中,我们的目的是探讨和比较异丙酚和右美托咪定对内毒素血症引起的脑病的影响，并研究是否涉及铁凋亡，最后为多药联合应用于脓毒症镇静提供实验依据。
■总共218只C57BL/6J雄性小鼠（20-25g，使用6-8周）。进行Morris水迷宫（MWM）测试以评估异丙酚和右美托咪定是否减轻LPS诱导的认知缺陷。使用Nissl和Fluoro-JadeC(FJC)染色评价脑损伤。通过二氢乙锭(DHE)和DCFH-DA染色以及通过测量三种细胞因子的水平来评估神经炎症。应用Iba1+和GFAP+细胞数目检测小胶质细胞和星形胶质细胞的活化。为了探索铁死亡的参与，ptgs2和chac1的水平；铁的含量，丙二醛（MDA），和谷胱甘肽（GSH）；并研究了铁凋亡相关蛋白的表达。
■单独使用丙泊酚和右美托咪定可减轻LPS诱导的认知障碍，而组合表现不佳。在减轻内毒素血症性神经丢失和变性方面，联合镇静剂组表现出最有效的能力。丙泊酚和右美托咪定均能抑制神经炎症，而异丙酚的作用稍弱。所有镇静组减少神经细胞凋亡，抑制小胶质细胞和星形胶质细胞的活化，减轻了神经上的铁性凋亡。合并组在对抗铁死亡的遗传和生化改变方面最为突出。Fpn1可能是内毒素血症相关铁凋亡激活的核心。
■总共218只C57BL/6J雄性小鼠（20-25g，使用6-8周）。进行Morris水迷宫（MWM）测试以评估异丙酚和右美托咪定是否减轻LPS诱导的认知缺陷。使用Nissl和Fluoro-JadeC(FJC)染色评价脑损伤。通过二氢乙锭(DHE)和DCFH-DA染色以及通过测量三种细胞因子的水平来评估神经炎症。应用Iba1+和GFAP+细胞数目检测小胶质细胞和星形胶质细胞的活化。为了探索铁死亡的参与，ptgs2和chac1的水平；铁的含量，丙二醛（MDA），和谷胱甘肽（GSH）；并研究了铁凋亡相关蛋白的表达。
■单独使用丙泊酚和右美托咪定可减轻LPS诱导的认知障碍，而组合表现不佳。在减轻内毒素血症性神经丢失和变性方面，联合镇静剂组表现出最有效的能力。丙泊酚和右美托咪定均能抑制神经炎症，而异丙酚的作用稍弱。所有镇静组减少神经细胞凋亡，抑制小胶质细胞和星形胶质细胞的活化，减轻了神经上的铁性凋亡。合并组在对抗铁死亡的遗传和生化改变方面最为突出。Fpn1可能是内毒素血症相关铁凋亡激活的核心。
