依托咪酯对脓毒症大鼠急性肺损伤的保护作用及其机制的研究  

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

作　　者：黄年丽 王运星 李英霞[1] 季兰馨 金艺华[1] Huang Nianli;Wang Yunxing;Li Yingxia;Ji Lanxin;Jin Yihua(The First Affiliated Hospital of Jiamusi University,Jiamusi,Heilongjiang 154000,China)

机构地区：[1]佳木斯大学附属第一医院,黑龙江佳木斯154000

出　　处：《感染、炎症、修复》2025年第2期98-101,共4页Infection Inflammation Repair

摘　　要：目的:探讨依托咪酯(ETO)对脓毒症大鼠急性肺损伤的保护作用及其作用机制与调控核转录因子红系2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路的关系。方法:取40只清洁级雄性SD大鼠,随机分成空白对照组、假手术组、脓毒症组[即盲肠结扎穿孔(CLP)组]、CLP+ETO组、CLP+ETO+ML385组(ML385为Nrf2抑制剂),每组8只,进行1周的适应性饲养。空白对照组未接受手术处理;假手术组大鼠行假手术处理;其他各组均通过CLP方法构建大鼠脓毒症模型并给予相应的药物干预,其中ETO于术前30 min腹腔注射,ML385于术后立即腹腔注射。于模型制备后18 d,采用酶联免疫吸附法测定各组血清肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)含量;取肺组织标本,采用苏木素-伊红染色评估其病理损伤状况并进行肺组织病理损伤评分,Western Blot法检测Nrf2和HO-1的蛋白表达。结果:ETO能够缓解CLP引起的小鼠肺水肿和肺组织病理变化,降低血清中炎症因子TNF-α和IL-1β的水平(P<0.05);同时上调Nrf2和HO-1的蛋白表达(P<0.05);给予ML385逆转了ETO的作用,CLP+ETO+ML385组的TNF-α和IL-1β水平上升,病理损伤评分上升,Nrf2、HO-1蛋白表达含量下降(P<0.05)。结论:ETO可能通过调控Nrf2/HO-1信号通路缓解脓毒症诱导的肺组织损伤。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-αand 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-αand IL-1βwere 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.

关 键 词：脓毒症 肺损伤 急性 依托咪酯 核转录因子红系2相关因子2 血红素加氧酶1 

分 类 号：R631[医药卫生—外科学]