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

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1 h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。

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

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.  ［Key words］sevoflurane; lipopolysaccharide; acute lung injury; postconditioning; inducible nitric oxide synthase; nitric oxide