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帕瑞昔布钠对呼吸机相关性肺损伤小鼠肺泡巨噬细胞表型转化的影响 被引量:1

Effect of parecoxib sodium on phenotypic transformation of alveolar macrophages in a mouse model of ventilator-associated lung injury
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摘要 目的评价帕瑞昔布钠对呼吸机相关性肺损伤(VALI)小鼠肺泡巨噬细胞表型转化的影响。方法SPF级健康成年雄性C57BL/6J小鼠45只,体重22~30 g,8~12周龄。采用随机数字表法分为3组(n=15):假手术组(S组)、VALI组(V组)和帕瑞昔布钠组(P组)。小鼠腹腔注射LPS 20 ng,2 h后采用机械通气(潮气量30 ml/kg,通气频率70次/min,吸呼比1∶2,吸入氧浓度21%,呼气末正压0)4 h的方法制备小鼠VALI模型。P组机械通气前1 h静脉注射帕瑞昔布钠30 mg/kg。于机械通气4 h时处死小鼠,生理盐水灌洗右肺收集肺泡灌洗液(BALF),采用ELISA法检测IL-6、IL-10和TNF-α浓度,采用Western blot法检测BALF诱导型一氧化氮合酶(iNOS)、精氨酸酶1(Arg-1)及肺泡巨噬细胞磷酸化酪氨酸激酶2(p-JAK2)和信号转导与转录激活因子3(p-STAT-3)的表达;取左肺确定湿重/干重(W/D)比值,观察肺组织病理学结果并行肺损伤评分。结果与S组比较,V组和P组肺损伤评分、W/D比值、BALF IL-6、IL-10和TNF-α浓度、iNOS、Arg-1、p-JAK2和p-STAT-3表达水平升高(P<0.05);与V组比较,P组BALF IL-10浓度、Arg-1、p-JAK2和p-STAT-3表达水平升高,肺损伤评分、W/D比值、BALF IL-6、TNF-α浓度和iNOS表达水平降低(P<0.05)。结论帕瑞昔布钠促进肺泡巨噬细胞由M1型向M2型转化,抑制炎症反应,从而减轻小鼠VALI,可能与活化JAK2/STAT-3信号通路有关。 Objective To evaluate the effect of parecoxib sodium on phenotypic transformation of alveolar macrophages in a mouse model of ventilator-associated lung injury(VALI).Methods Forty-five SPF healthy adult male C57BL/6J mice,weighing 22-30 g,aged 8-12 weeks,were divided into 3 groups(n=15 each)using a random number table method:sham operation group(S group),VALI group(V group)and parecoxib sodium group(P group).Lipopolysaccharide 20 ng was intraperitoneally injected,and 2 h later the animals were mechanically ventilated(tidal volume 30 ml/kg,respiratory rate 70 breaths/min,inspiratory/expiratory ratio 1∶2,fraction of inspired oxygen 21%,positive end-expiratory pressure 0)for 4 h to establish the model of VALI.Parecoxib sodium 30 mg/kg was intravenously injected at 1 h prior to mechanical ventilation in group P.The mice were sacrificed at 4 h of ventilation,the right lung was lavaged and the broncho-alveolar lavage fluid(BALF)was collected for determination of interleukin-6(IL-6),IL-10 and tumor necrosis factor-alpha(TNF-α)concentrations(by enzyme-linked immunosorbent assay),expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)in BALF and expression of phosphorylated Janus kinase 2(p-JAK2)and phosphorylated signal transduction and transcription activator 3(p-STAT-3)(by Western blot).The left lung was removed for determination of the wet/dry weight ratio(W/D ratio)and for examination of the pathological changes which were scored.Results Compared with group S,the lung injury score,W/D ratio,concentrations of IL-6,IL-10 and TNF-αin BALF,and expression of iNOS,Arg-1,p-JAK2 and p-STAT-3 were significantly increased in V and P groups(P<0.05).Compared with group V,the concentration of IL-10 in BALF and expression of Arg-1,p-JAK2 and p-STAT-3 were significantly increased,and the lung injury score,W/D ratio,concentrations of IL-6 and TNF-αin BALF and expression of iNOS were decreased in group P(P<0.05).Conclusion Parecoxib sodium promotes phenotypic transformation of alveolar macrophages from M1 subtype to M2 subtype and inhibits inflammatory responses,thus alleviating VALI,which may be related to activating JAK2/STAT-3 signaling pathway in mice.
作者 张超锋 柴小青 王迪 胡姗姗 许辉 胡继成 魏昕 疏树华 魏伟 Zhang Chaofeng;Chai Xiaoqing;Wang Di;Hu Shanshan;Xu Hui;Hu Jicheng;Wei Xin;Shu Shuhua;Wei Wei(Department of Anesthesiology,Affiliated Provincial Hospital,Anhui Medical University,Hefei 230001,China;Anhui Medical University,Institute of Clinical Pharmacology,Hefei 230001,China)
出处 《中华麻醉学杂志》 CAS CSCD 北大核心 2020年第3期369-372,共4页 Chinese Journal of Anesthesiology
基金 国家自然科学基金青年科学基金项目(81503080) 安徽省重点研究与开发计划项目(1804h08020286)。
关键词 环氧化酶2抑制剂 呼吸机相关性肺损伤 巨噬细胞 肺泡 表型 Cyclooxygenase 2 inhibitors Ventilator-induced lung injury Macrophages,alveolar Phenotype
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