法舒地尔对脂多糖诱导的急性肺损伤大鼠的保护作用

目的探讨法舒地尔(fasudil)对脂多糖(LPS)诱导的急性肺损伤(ALI)大鼠的保护作用。方法45只雄性SD大鼠随机分为三组:对照组(NS组,n=15)、脂多糖组(LPS组,n=15)及法舒地尔干预组(FAS组,n=15),LPS组和FAS组采用股静脉注射LPS(5 mg/kg)建立ALI模型,FAS组在LPS注射前30 min腹膜内注射法舒地尔(10 mg/kg)。在3 h、6 h、12 h三个时间点通过血气分析、肺湿/干重比(W/D)、肺组织HE染色观察急性肺损伤的程度,酶联免疫吸附法(ELISA)检测血清中肿瘤坏死因子-a(TNF-a)和白介素-1β(IL-1β)水平。结果与LPS组相比,法舒地尔组在LPS注射后3 h、6 h和12 h时间点PaO2较LPS组显著升高(P<0.05),而肺组织W/D比值、肺损伤评分、血清TNF-α和IL-1β水平显著降低(P<0.05)。结论法舒地尔可以减轻脂多糖诱导的急性肺损伤大鼠的肺损伤程度,其机制可能与抑制致炎因子TNF-α和IL-1β的释放有关。

The Protective effect of fasudil on acute lung injury induced by lipopolysaccharide in rats

Objective To explore the potential protective effect of fasudil on acute lung injury （ALI） induced by lipopolysaccharide in rats. Methods A total of 45 male SD rats were randomly divided into three groups： control group （ NS group n = 15 ）, lipopolysaccharide group （ LPS group n = 15 ） and fasudil treatment group （ FAS group n = 15）. The all model was established by injecting LPS intravenously （5 mg/kg） in the LPS group and the FAS group. The FAS group was injected intraperitoneally with fasudil （10 mg/kg） thirty minutes before LPS injection. Tumor necrosis factor-α （TNF-α） and interleukin （IL） 1β （IL-1 beta） level in serum were measured through ELISA method, the blood gas analysis, lung tissue wet/dry weight ratio （W/D） ,lung tissue HE dyeing were tested in 3 h,6 h,12 h three time points after LIPS injection. Results In comparison with the LPS group,the arterial partial pressure of oxygen（PaO2） was significantly increased （P 〈 0. 05 ） and the ratio of lung tissue wet/dry weight （W/ D） ,Lung Injury Score and the levels of TNF-α and IL-1β in serum were significantly decreased（ P 〈 0.05 ） in the FAS group in 3 h,6 h,12 h three time points after LPS injection. Conclusion Fasudil has a beneficial effect on the IS＇S-induced acute lung injury of rats, which may be related to its effect in inhibiting the proimqammatory cytokines release of TNF-α and IL-1β.