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目的：急性肺损伤是临床上常见的危重病，发病急，死亡率高，目前仍缺乏有效的治疗手段，新型的外源性硫化氢供体 GYY4137 具有抗炎、抗休克、抗癌及抗血栓等作用，本研究探讨其对脂多糖诱导的小鼠急性肺损伤的保护作用及其机制。方法：将BALB/c 小鼠(18-20 g)随机分为3 组：正常对照组(20 只)，脂多糖组(20 只)，治疗组(20 只)，然后复制小鼠脂多糖诱导的急性肺损伤模型：给予小鼠腹腔注射脂多糖(10 mg/ kg) 复制小鼠急性肺损伤模型模型，治疗组注射脂多糖1 小时后给予腹腔注射 GYY4137 (50 mg/ kg)，在给予脂多糖8 小时后将小鼠处死，留取血清与组织标本。检测小鼠血清中的炎症因子肿瘤坏死因子alpha、白介素6 及白介素10 的表达，检测小鼠血清中H2S 的含量，测得肺脏湿/ 干比，检测肺组织中的髓过氧化物酶活性，并测得肺组织中与氧化应激相关的H2O2、·OH 与SOD因子的含量。结果：脂多糖引起了严重的肺损伤，GYY4137 对脂多糖导致的肺水肿、炎症反应及氧化应激损伤有不同程度的改善，保护了脂多糖造成的肺损伤，降低了脂多糖诱导的小鼠肺脏氧化应激损伤。其保护作用于抗炎、抗氧化有关。结论：GYY4137 可能通过抗炎、抗氧化作用途径保护了脂多糖造成的急性肺损伤，可能在炎症疾病模型中也发挥相同作用，并且为未来临床使用缓释硫化氢供体提供了基础资料。

英文摘要:

Objective:Acute lung injury is a common severe disease clinically which characterized with urgent oncoming and high death rate. There are short of effective therapeutic methods treating acute lung injury. GYY4137, a new exogenous hydrogen sulfide donor, was shown to possess anti-inflammation, anti-shock, anti-cancer, and anti-thrombus effects. This study was to investigate the protective effects of GYY4137 on LPS induced acute lung injury and the mechanisms underlying.Methods:BALB/c mice (18-20 g) were randomly designated into 3 groups: normal control group (20), LPS treated group (20), and GYY4137 treatment group. The mice of acute lung injury group received an intraperitoneal administration of LPS (10 mg/kg). The mice of GYY4137 treatment group received a dose of GYY4137 (50 mg/ kg, i.p.) after administration of LPS for an hour. The mice were sacrificed 8 hours after LPS treatment for. Serum samples and lung tissues were collected. The inflammatory cytokines of tumor necrosis factor alpha, interleukin 6, and interleukin 10 were analyzed. The concentration of H2S in mice plasma was analyzed. The wet to dry ratio and myeloperoxidase activity of mice lungs was detected. The oxidative stress related factors H2O2,·OH, and SOD concentrations in mice lungs were also checked.Results:LPS induced severe acute lung injury. GYY4137 administration decreased lung edema, inflammatory response, and oxidative damages resulted by LPS. Treatment of GYY4137 protected LPS induced lung injuries, and the protective effects of GYY4137 may contribute to its anti-inflammation and anti-oxidative effects.Conclusion:GYY4137 protected mice from LPS-induced acute lung injury which may be related with its anti-inflammation and anti-oxidative effects. The slow-releasing H2S donors may also exert the same activities in other models of inflammation, and may offer new basic information for clinical application.

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