法舒地尔对脂多糖诱导的急性肺损伤大鼠的保护作用

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

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。

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.