Protective effect of etomidate on acute lung injury in septic rats and its mechanism

Huang Nianli; Wang Yunxing; Li Yingxia; Ji Lanxin; Jin Yihua

doi:10.3969/j.issn.1672-8521.2025.02.005

Abstract：Objective:To explore the protective effect of etomidate(ETO)on acute lung injury in septic rats and the relationship between its mechanism of action and the regulation of the nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)signaling pathway.Methods:Forty clean male Sprague-Dawley rats were randomly divided into five groups:the blank control group,sham surgery group,sepsis group[cecal ligation and puncture(CLP)group,animal model of sepsis lung injury was prepared by CLP],CLP+ETO group,CLP+ETO+ML385 group(ML385 is Nrf2 inhibitor),with 8 rats in each group.The rats were acclimatized for one week.The blank control group received no special treatment,and the sham surgery group underwent sham surgery.The other groups were subjected to CLP to induce sepsis model and given corresponding drug intervention.Serum levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were measured by enzyme-linked immunosorbent assay(ELISA)18 days after the model was prepared.The pathological injury status of lung tissue was evaluated by hematoxylin-eosin staining,and the pathological injury score of lung tissue was performed.The protein expression levels of Nrf2 and HO-1 in the lung tissue were detected using Western Blot.Results:Etomidate alleviated lung edema and pathological changes in the lungs of rats induced by CLP,reduced the levels of serum inflammatory factors TNF-α and IL-1β(P＜0.05).Meanwhile,the expression of Nrf2 and HO-1 protein was upregulated(P＜0.05).In the CLP+ETO+ML385 group,the levels of TNF-α and IL-1β were increased,the pathological injury scores were increased,and Nrf2 and HO-1 protein expression levels were decreased(P＜0.05).Conclusions:Etomidate may exert its protective effect on sepsis-induced lung tissue damage by regulating the Nrf2/HO-1 signaling pathway.