Isoflurane Preconditioning Ameliorates Endotoxin-Induced Acute Lung Injury and Mortality in Rats
Isoflurane Preconditioning Ameliorates Endotoxin-Induced Acute Lung Injury and Mortality in Rats
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DOI：
10.1213/ane.0b013e3181baf506
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发表时间：
2009-11-01
影响因子：
5.7
通讯作者：
Sun, Yu
中科院分区：
文献类型：
--
作者：
Li, Qi Fang;Sen Zhu, Ye;Sun, Yu
背景技术背景：异氟醚预处理对严重内毒素诱导的急性肺损伤（ALI）中肺促炎细胞因子和存活率的影响尚未进行系统研究。方法：将体重250-300 g的雄性SD大鼠随机分为4组：假手术组（Sham）、吸入异氟醚（Isoflurane）组（Isoflurane）、吸入异氟醚（Isoflurane）组（Isoflurane）和吸入异氟醚（Isoflurane（用生理盐水腹膜内[IP]注射）用溶剂预处理（100%O-2）（假-媒介物）;用异氟烷预处理的假大鼠（假-ISO）;用媒介物预处理的LPS大鼠（用LPS IP注射）（媒介物-LPS）;和用异氟烷预处理的LPS大鼠（ISO-LPS）。腹腔注射LPS诱导内毒素血症。注射LPS前30 min给予1.4%异氟烷。然后观察动物6 h。我们监测了动脉血压，心率和血气。通过肺湿/干比、伊文思蓝渗出和组织学检查评估ALI的程度。我们还测量了肺一氧化氮（NO）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1 β和IL-6水平。此外，生存统计和肺诱导型一氧化氮合酶（iNOS）基因表达也determined.RESULTS：LPS引起全身性低血压和严重的ALI，证明了在ALI的程度，肺功能受损的增加，肺NO，TNF-α，IL-1 β，IL-6的增加。异氟醚预处理可减轻全身性低血压和ALI的发生。异氟醚预处理还减弱了LPS诱导的肺硝酸盐/亚硝酸盐和促炎细胞因子释放的增加，并改善了严重脓毒症大鼠的生存率。结论：异氟醚预处理可减少脓毒症大鼠肺组织中促炎细胞因子的释放，降低脓毒症大鼠死亡率。早期保护似乎部分通过抑制iNOS-NO途径活化来介导。（Anesth Analg 2009;109：1591-7）
BACKGROUND: The effects of isoflurane pretreatment on pulmonary proinflammatory cytokines and survival in severe endotoxin-induced acute lung injury (ALI) have not been studied systemically. We investigated the effect of preadministration of isoflurane on ALI induced by lipopolysaccharide (LPS) in rats.METHODS: Male Sprague-Dawley rats weighing 250-300 g were randomly assigned to 1 of 4 groups: sham rats (injected intraperitoneally [IP] with saline) pretreated with vehicle (100% O-2) (sham-vehicle); sham rats pretreated with isoflurane (sham-ISO); LPS rats (injected IP with LPS) pretreated with vehicle (vehicle-LPS); and LPS rats pretreated with isoflurane (ISO-LPS). Endotoxemia was induced by IP injection of LPS. Isoflurane 1.4% was administered 30 min before LPS injection. The animals were then observed for 6 h. We monitored arterial blood pressure, heart rate, and blood gas. The extent of ALI was evaluated by lung wet/dry ratio, Evans blue dye extravasation, and histologic examination. We also measured pulmonary nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 levels. In addition, survival statistics and pulmonary inducible NO synthase (iNOS) gene expression were also determined.RESULTS: LPS caused systemic hypotension and severe ALI, as evidenced by the increases in the extent of ALI, impairment of pulmonary functions, and increases in pulmonary NO, TNF-alpha, IL-1 beta, and IL-6. Isoflurane preconditioning mitigated systemic hypotension and the development of ALI. Isoflurane preconditioning also attenuated the LPS-induced increases in pulmonary nitrate/nitrite and proinflammatory cytokine release and improved survival of rats with severe sepsis. The expression of iNOS was upregulated by LPS and reduced by isoflurane pretreatment.CONCLUSIONS: Isoflurane preconditioning can attenuate pulmonary proinflammatory cytokine release and decrease the mortality induced by severe sepsis. Early protection seems to be mediated partly through inhibition of iNOS-NO pathway activation. (Anesth Analg 2009;109:1591-7)