Dong Xiang, Hu Rong, Sun Yu, Li Qifang, Jiang Hong
Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Exp Lung Res. 2013 Sep;39(7):295-303. doi: 10.3109/01902148.2013.817627. Epub 2013 Aug 6.
Isoflurane (ISO) has been shown to attenuate acute lung injury (ALI). Induction of heme oxygenase-1 (HO-1) and suppression of inducible nitric oxide synthase (iNOS) expression provide cytoprotection in lung and vascular injury. The aim of this study was to investigate the effect of post-treatment with isoflurane on lung vascular permeability and the role of HO-1 in an ALI rat model induced by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly assigned to one of four groups: sham group, sham rats post-treated with vehicle (Sham); CLP group, CLP rats post-treated with vehicle (CLP); ISO group, CLP rats post-treated with isoflurane (ISO); and ZnPP group, CLP rats injected with zinc protoporphyrin IX (ZnPP), a competitive inhibitor of HO-1, 1 hour before the operation, and post-treated with isoflurane (ZnPP). Isoflurane (1.4%) was administered 2 hour after CLP. At 24 hour after CLP, the extent of ALI was evaluated by lung wet/dry ratio, Evans blue dye (EBD) extravasation, lung permeability index (LPI), as well as histological and immunohistochemical examinations. We also determined pulmonary iNOS and HO-1 expression. Compared with the CLP group, the isoflurane post-treatment group showed improved pulmonary microvascular permeability as detected by EBD extravasation, LPI, as well as histological and immunohistochemical examinations. Furthermore, isoflurane decreased iNOS and increased HO-1 expression in lung tissue. Pretreatment with ZnPP prevented the protective effects of isoflurane in rats. These findings indicate that the protective role of isoflurane post-conditioning against CLP-induced lung injury may be associated with its role in upregulating HO-1 in ALI.
异氟烷（ISO）已被证明可减轻急性肺损伤（ALI）。血红素加氧酶-1（HO-1）的诱导和诱导型一氧化氮合酶（iNOS）表达的抑制在肺和血管损伤中提供细胞保护作用。本研究的目的是探讨异氟烷后处理对肺血管通透性的影响以及HO-1在盲肠结扎和穿刺（CLP）诱导的ALI大鼠模型中的作用。雄性Sprague-Dawley大鼠随机分为四组之一：假手术组，假手术大鼠用溶剂后处理（假手术组）；CLP组，CLP大鼠用溶剂后处理（CLP组）；ISO组，CLP大鼠用异氟烷后处理（ISO组）；以及ZnPP组，CLP大鼠在手术前1小时注射HO-1的竞争性抑制剂原卟啉锌IX（ZnPP），并用异氟烷后处理（ZnPP组）。CLP后2小时给予异氟烷（1.4%）。CLP后24小时，通过肺湿/干比、伊文思蓝染料（EBD）外渗、肺通透性指数（LPI）以及组织学和免疫组织化学检查评估ALI的程度。我们还测定了肺组织中iNOS和HO-1的表达。与CLP组相比，异氟烷后处理组通过EBD外渗、LPI以及组织学和免疫组织化学检查显示肺微血管通透性得到改善。此外，异氟烷降低了肺组织中iNOS的表达并增加了HO-1的表达。ZnPP预处理可阻止异氟烷对大鼠的保护作用。这些发现表明，异氟烷后处理对CLP诱导的肺损伤的保护作用可能与其在ALI中上调HO-1的作用有关。
