Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice
Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice
复制标题
DOI：
10.1097/ccm.0b013e3181847b43
复制
发表时间：
2008-09-01
影响因子：
8.8
通讯作者：
Rocco, Patricia R. M.
中科院分区：
文献类型：
--
作者：
Leite-Junior, Jose Henrique P.;Garcia, Cristiane S. N. B.;Rocco, Patricia R. M.
目的：已提出Gorticosteroids是有效地调节炎症反应和肺组织重塑在急性肺损伤（ALI）。我们假设，类固醇治疗可能会采取不同的肺（p）或肺外（exp）ALI与类似的机械compromise.Design模型：前瞻性，随机，对照实验study.Setting：大学研究实验室。主题：一百二十八BALB/c小鼠（20-25克）。干预：小鼠被分为六组。在对照组动物中，经气管内（0.05 mL，Cp）或腹膜内（0.5 mL，Gexp）注射无菌盐水溶液，而ALI动物经气管内（10 μ g，ALIp）或腹膜内（125 μ g，ALIexp）注射大肠杆菌脂多糖。脂多糖给药后6小时，ALIp和ALlexp动物进一步随机分为接受生理盐水（0.1 mL静脉注射）或甲泼尼龙（2 mg/kg静脉注射，Mp和Mexp，分别）的亚组。测量和主要结果：在24小时，肺状态弹性，阻力和粘弹性压力，肺形态测量，和胶原纤维含量在两个ALI组相似。支气管肺泡灌洗液中的KC、白细胞介素-6和转化生长因子（TGF）-β水平，以及肿瘤坏死因子（TNF）-α、迁移抑制因子（MIF）、干扰素（IFN）-γ、肺组织中的TGF-β 1和TGF-β 2信使RNA表达在ALIP中高于ALIexpp动物。甲泼尼龙仅在ALIP动物中减弱了机械和形态测量变化、细胞因子水平以及TNF-α、MIF、IFN γ和TGF-β 2信使RNA表达，但阻止了两个ALI组中胶原纤维含量的任何变化。结论。甲基强的松龙可有效抑制纤维化，与ALI的病因无关，但其减轻炎症反应和肺机械变化的能力因ALI的病因而异。
Objective: Gorticosteroids have been proposed to be effective in modulating the inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI). We hypothesized that steroid treatment might act differently in models of pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise.Design: Prospective, randomized, controlled experimental study.Setting: University research laboratory.Subjects: One hundred twenty-eight BALB/c mice (20-25 g).Interventions: Mice were divided into six groups. In control animals sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally (0.5 mL, Gexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 mu g, ALIp) or intraperitoneally (125 mu g, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALlexp animals were further randomized into subgroups receiving saline (0.1 mL intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp, respectively).Measurements and Main Results: At 24 hrs, lung state elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interieukin-6, and transforming growth factor (TGF)-beta levels in bronchoatveolar lavage fluid, as well as tumor necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)-gamma, TGF-beta 1 and TGF-beta 2 messenger RNA expression in lung tissue were higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical and morphometric changes, cytokine levels, and TNF-alpha, MIF, IFN gamma, and TGF-beta 2 messenger RNA expression only in ALIp animals, but prevented any changes in collagen fiber content in both ALI groups.Conclusions. Methylprednisolone is effective to inhibit fibrogenesis independent of the etiology of ALI, but its ability to attenuate inflammatory responses and lung mechanical changes varies according to the cause of ALI.