摘要
目的:探讨艾司氯胺酮是否通过调控miR-146a表达对脓毒症(sepsis)诱发的急性肺损伤(acute lung injury,ALI)发挥保护作用。方法:通过脂多糖(lipopolysaccharide,LPS)(10 mg/kg)诱导建立脓毒症急性肺损伤小鼠模型,使用气管滴注和腹腔注射两种方法评估效果。检测病理组织切片肺组织炎症变化、测定肺湿重/干重比(W/D);酶联免疫吸附法检测肺泡灌洗液中白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和IL-1β含量;qRT-PCR检测肺组织中miR-146a、IL-6、TNF-β和IL-1β的表达水平。结果:艾司氯胺酮可以减轻LPS诱导的脓毒症急性肺损伤小鼠的肺损伤程度,且可显著抑制肺泡灌洗液及肺组织中IL-6、TNF-α和IL-1β的表达,同时上调miR-146a水平。结论:艾司氯胺酮可能通过激活miR-146a表达,抑制NF-κB通路介导的炎症反应,从而减轻脓毒症ALI,其中腹腔注射途径效果更优,为临床治疗提供了潜在策略。
Objective To investigate whether esketamine exerts a protective effect against sepsis-induced acute lung injury(ALI)by regulating miR-146a expression.Methods A sepsis-induced ALI mouse model was established using lipopolysaccharide(LPS,10 mg/kg).The therapeutic efficacy of esketamine was assessed via two administration routes:intratracheal instillation and intraperitoneal injection.Pathological changes in lung tissue were evaluated by histopathological examination.The lung wet/dry weight ratio(W/D)was calculated to assess pulmonary edema.Levels of IL-6,TNF-α,and IL-1βin bronchoalveolar lavage fluid(BALF)were measured by enzyme-linked immunosorbent assay(ELISA).The expression levels of miR-146a,IL-6,TNF-β,and IL-1βin lung tissues were quantified via qRT-PCR.Results Esketamine alleviated LPS-induced lung injury in septic mice and significantly suppressed the expression of IL-6,TNF-α,and IL-1βin BALF and lung tissues.Concurrently,esketamine upregulated miR-146a levels.Conclusion Esketamine mitigates sepsis-induced ALI by activating miR-146a expression and suppressing NF-κB pathway-mediated inflammatory responses.Intraperitoneal administration demonstrated superior efficacy compared to intratracheal instillation,highlighting its potential as a clinical therapeutic strategy.
作者
杨雯宇
禹枫
李模勇
张晶晶
陈安基
YANG Wenyu;YU Feng;LI Moyong;ZHANG Jingjing;CHEN Anji(Changsha Hospital for Maternal&Child Health Care Affiliated to Hunan Normal University,Changsha 410007;College of Life Sciences,Hunan Normal University,Changsha 410081;Hunan Aerospace Hospital Affiliated to Hunan Normal University,Changsha 410013)
出处
《晓庄学院学报(医学版)》
2025年第3期15-19,共5页
Journal of Hunan Normal University(Medical Sciences)
基金
长沙市自然科学基金“艾司氯胺酮对脓毒症ALI小鼠IRAKI和TRAF6表达的影响”(kq2208477)
