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。
Abstract
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-1β in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of miR-146a, IL-6, TNF-β, and IL-1β in 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-1β in 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.
关键词
艾司氯胺酮 /
miR-146a /
脓毒症 /
急性肺损伤 /
腹腔注射
Key words
esketamine /
miR-146a /
sepsis /
acute lung injury /
intraperitoneal injection
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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）
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