七氟烷后处理对脂多糖致急性肺损伤大鼠iNOS/NO通路的影响

Effects of postconditioning with sevoflurane on iNOS/NO pathway in rats with acute lung injury induced by lipopolysaccharide

目的:探讨七氟烷后处理对脂多糖(lipopolysaccharide,LPS)致急性肺损伤大鼠诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)/NO通路的影响及作用机制。方法:将30只大鼠随机均分为5组,生理盐水组和脂多糖组分别于气管内滴注生理盐水(1 mL/kg)或脂多糖(5 mg/kg);七氟烷0.5,1,2 h组于气管内滴注脂多糖4 h后,即急性肺损伤发生,分别吸入2.4%七氟烷0.5,1,2 h,模拟"后处理"方案。6 h后处死大鼠,取肺组织,行HE染色,观察病理变化;免疫组织化学法测iNOS表达;硝酸还原酶法测NO含量。结果:与生理盐水组相比,脂多糖组肺泡腔内有大量炎性细胞浸润,肺间质及肺泡腔有严重的水肿、出血,肺泡结构破坏严重。七氟烷组肺组织损伤较脂多糖组明显减轻。脂多糖组肺组织内iNOS蛋白表达和NO含量较生理盐水组明显升高(P均<0.01);七氟烷组iNOS蛋白表达和NO含量较脂多糖组明显降低(P<0.01或P<0.05),以七氟烷1h组和七氟烷2 h组下降更明显(P<0.05)。结论:七氟烷后处理可减轻脂多糖所致大鼠急性肺损伤,其机制可能与抑制iNOS/NO信号通路的激活,减轻炎症反应有关。

Objective:To investigate the effects of postconditioning with sevoflurane on inducible nitric oxide synthase(iNOS)/nitric oxide(NO) pathway in rats with acute lung injury induced by lipopolysaccharide.Methods:Thirty rats were randomly divided into 5 groups(n = 6),NS group and LPS group,rats received intratracheal instillation of normal saline(1 mL/kg) and lipopolysaccharide(5 mg/kg),respectively;sevoflurane groups(S 0.5,1,2 h),4 h after lipopolysaccharide intratracheal instillation(i.e.after the occurrence of acute lung injury),rats received sevoflurane inhalation(2.4%) for 0.5,1,2 h,respectively,simulating a postconditioning scheme.Lung tissue samples were harvested 6 h after normal saline or lipopolysaccharide intratracheal instillation.Histological examination by light microscopy was performed;iNOS expression and NO concentration in lung parenchyma were measured by immunohistochemistry and with NO Assay Kit.Results:Compared with the NS group,iNOS expression and NO concentration in the LPS group were significantly increased(P < 0.01),with more severe lung injury.Compared with the LPS group,iNOS expression and NO concentration in S groups were greatly reduced(P < 0.01 or P < 0.05),with attenuated lung injury,especially in S1h and S2h groups.Conclusion:Postconditioning with sevoflurane could attenuate lipopolysaccharide-induced acute lung injury in rats through inhibiting iNOS/NO pathway activation and reducing the inflammatory response.