艾司莫酮在脓毒症诱导的脑损伤小鼠中抑制认知损伤和神经炎症。
Esmolol inhibits cognitive impairment and neuronal inflammation in mice with sepsis-induced brain injury.
发表日期:2023 Jan 01
作者:
Yanpeng Li, Junli Ma, Jianjun Diao, Wei Chen, Zhihua Wang
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
败血症是一种因机体对感染作出失调反应导致的潜在致命器官衰竭病症。由于医疗护理的高昂费用,它对家庭和社会造成了巨大的经济负担。本研究旨在探究依舒莫尔(Esmolol)在败血症诱导的脑损伤小鼠中对认知功能障碍和神经炎症的保护作用。雄性C57BL/6J小鼠经腹腔注射脂多糖(10mg/kg,L2630,Sigma)建立败血性脑病模型。在注射脂多糖前,使用渗透微泵亚皮下注入依舒莫尔(15mg/kg/h,HY-B1392,MedChemExpress)进行连续6小时。通过莫里斯水迷宫和新物体辨识测试评估脂多糖引起的认知功能障碍和行为表型。使用ELISA和RT-qPCR检测细胞因子和蛋白表达。依舒莫尔治疗潜在地改善败血症小鼠的认知障碍。依舒莫尔治疗明显改善了异常的海马神经元结构,并显著下调了海马组织中白介素(IL)-1β、IL-6和肿瘤坏死因子-α的表达。依舒莫尔治疗显著减少了凋亡TUNEL阳性细胞,并恢复了相关基因表达(BAX和BCL-2)。依舒莫尔对反应性氧化物和氧化应激的影响显著降低了海马组织中丙二醛(MDA)含量,增加了超氧化物歧化酶和过氧化氢酶的含量。此外,依舒莫尔显著减少了败血症小鼠中Iba-1+小胶质细胞的百分比和密度。我们的结果表明,依舒莫尔潜在地改善了败血症诱导的脑损伤小鼠的认知功能障碍和神经炎症。(作者于2023年,由德古意特出版社发表)
Sepsis is a potentially fatal organ failure resulting from a dysregulated host response to infection. It can be a substantial financial burden on families and society due to the high cost of medical care. The study aims to investigate the protective roles of Esmolol in mice with sepsis-induced brain injuries against cognitive dysfunction and neuronal inflammation. Male C57BL/6J mice were intraperitoneally injected with LPS (10 mg/kg, L2630, Sigma) to establish a septic encephalopathy model. Esmolol (15 mg/kg/h, HY-B1392, MedChemExpress) was subcutaneously infused using osmotic mini-pumps for 6 h before LPS injection. Morris water maze and novel object recognition tests evaluated LPS-induced cognitive impairment and behavioral phenotypes. Cytokines and protein expression were assessed using ELISA assay and RT-qPCR. Esmolol treatment potentially improved cognitive impairment in septic mice. Esmolol administration markedly diminished the abnormal hippocampal neuronal structure, and the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α was significantly downregulated in the hippocampal tissue. Esmolol treatment significantly reduced apoptotic TUNEL-positive cells and reversed the related gene expression (BAX and BCL-2). The effects of esmolol on the reactive oxidative species and oxidative stress markedly reduce malondialdehyde MDA content and increase superoxide dismutase and catalase in hippocampal tissues. In addition, esmolol significantly reduced the percentage and density of Iba-1 + microglia in septic mice. Our results demonstrated that esmolol potentially improved cognitive impairment and neuronal inflammation in mice with sepsis-induced brain injury.© 2023 the author(s), published by De Gruyter.