保护素DX 对脓毒症小鼠急性肺损伤的保护作用

Protective effect of protectin DX on acute lung injury in mouse model of sepsis

摘要:

目的 探讨保护素DX（PDX）对小鼠脓毒症所致急性肺损伤的保护作用。方法 45 只健康雄性昆明 小鼠利用随机数字表随机分为假手术组、脓毒症组和PDX 干预组，每组15 只，复制小鼠脓毒症模型，术毕 60 min 后，PDX 干预组小鼠腹腔注射1 μg 的PDX，假手术组和脓毒症组则给予等量的生理盐水，建模24 h 后， 处死各组小鼠，观察各组小鼠肺组织病理学变化，检测各组小鼠肺组织中白细胞介素1β（IL-1β）、白细胞介 素6（IL-6）及肿瘤坏死因子α（TNF-α）、超氧化物歧化酶（SOD）、丙二醛（MDA）水平，Western blot 检 测肺组织胞核中核因子κB（NF-κB）和胞浆中核因子κB 抑制蛋白α 抗原（IκB-α）蛋白表达。结果 与 假手术组比较，脓毒症组和PDX 干预组小鼠肺组织损伤组织学评分均升高，与脓毒症组比较，PDX 干预组 小鼠肺组织损伤组织学评分则降低，差异有统计学意义（F =253.323，P =0.000）；与假手术组比较，脓毒症组和 PDX 干预组小鼠肺组织中IL-1β、IL-6、TNF-α、SOD 及MDA 水平均升高，差异有统计学意义（P <0.05）， 与脓毒症组比较，PDX 干预组小鼠肺组织中IL-1β、IL-6、TNF-α、SOD 及MDA 水平均降低，差异有统计 学意义（P <0.05）；与假手术组比较，脓毒症组和PDX 干预组小鼠肺组织胞核中NF-κB 蛋白相对表达量均 升高，而胞浆中IκB-α 蛋白相对表达量均降低，差异有统计学意义（P <0.05）；与脓毒症组比较，PDX 干 预组小鼠肺组织胞核中NF-κB 蛋白相对表达量均降低，而胞浆中IκB-α 蛋白相对表达量均升高，差异有 统计学意义（P <0.05）。结论 PDX 可减轻脓毒症所致小鼠肺组织损伤，其机制与减轻氧化应激反应及通过 调控NF-κB/IκB-α 通路而抑制炎症因子释放有关。

Abstract:

Objective To investigate the protective effect of protectin DX (PDX) on acute lung injury (ALI) in mouse model of sepsis. Methods Totally 45 healthy male Kunming mice were randomly divided into sham group, sepsis group and PDX group. Sepsis model was prepared with standard protocol. At the 60th min post surgery, mice in PDX group was intraperitoneally injected with 1μg of PDX while mice in sham group and sepsis group received the same amount of normal saline. At the 60th post surgery, lungs were harvested. The histopathological change of lung tissue was scored. Levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were measured. Nuclear factor-κB (NF- κB) in the nucleus and nuclear factor κ B inhibiting α antigen (IκB-α) in the cytoplasm of lung tissue were identified by Western blot. Results Compared with sham operation group, ALI the score were increased in the sepsis group, which was attenuated significantly by PDX (F = 253.323, P = 0.000). Levels of IL-1β, IL-6, TNF-α, SOD and MDA in the lung tissues of sepsis group were increased compared with sham group, which was dramatically ameliorated with treatment of PDX (P < 0.05). Relative concentration of NF-κB in the nucleus upregulated while IκB-α in cytoplasm was down regulated in sepsis group when compared with sham group (P < 0.05), which was significantly diminished by PDX therapy (P < 0.05). Conclusion PDX protects sepsis inducecd lung injury through alleviating oxidative stress and inhibiting the NF-κB/IκB-α mediated release of inflammatory factors.