七氟醚对肺缺血-再灌注损伤兔的保护作用

Protective Effects of Sevoflurane Against Lung Ischemia-reperfusion Injury in Rabbits

目的探讨七氟醚对兔肺缺血-再灌注损伤的保护作用及可能机制。方法96只日本大耳白兔,随机分为4组(n=24):假手术组(S组)、缺血再灌注组(IR组)、七氟醚缺血-再灌注组(Sev-IR组)和七氟醚组(Sev-S)。IR组、Sev-IR组参照Epp inger方法建立肺缺血再灌注模型,Sev-IR组吸入肺泡最小有效浓度(MAC)七氟醚30 min后行缺血-再灌注,Sev-S组吸入1MAC七氟醚30 min后不进行缺血再灌注。分别在缺血45 min、再灌注60,120 min处死兔,行动脉血气分析,测定肺组织湿干重比(W/D)、TNFα、IL-1β和IL-10的含量以及MPO的活性、支气管肺泡灌洗液(BALF)中白细胞分类计数、肺通透性指数及肺组织病理学检查。结果再灌注后IR组和Sev-IR组的肺组织W/D、TNFα、IL-1β的含量以及MPO的活性、肺通透性指数、BALF中白细胞数、中性粒细胞数均高于S组(P<0.01),Sev-IR组减弱上述指标的升高(P<0.05);IR组和Sev-IR组IL-10低于S组(P<0.01),而Sev-IR组IL-10的含量明显高于IR组(P<0.05)。病理学检查显示七氟醚预先给药减弱肺组织缺血-再灌注损伤的程度。结论七氟醚对肺缺血-再灌注损伤兔有保护作用,其机制可能与其抑制TNF-α、IL-1β释放,升高IL-10的水平,抑制PMN的浸润有关。

Objective To investigate the protective effects and possible mechanisms of sevoflurane against ischemiareperfusion（I/R） injury on the lungs in rabbits. Methods Ninety six Japanese long-ear white rabbits weighting 2.5-3.0 kg were randomly divided into four groups （n =24 each） ： sham operation group（S） ; I/R group in which hilum of left lung was clamped for 45 min and then unclamped for reper-fusion 120 min ; Sev-I/R group 1MAC sevoflurane was inhaled for 30 min before ischemia , Sev -S group 1MAC sevoflurane was inhaled for 30 min without I/R. The changes of arterial blood gas analysis, the lung wet-to-dry weight ratio （W/D） , The tumor necrosis factorα （TNF-α） , interleukin-1 β （ IL-1 β） , interleukin-10 （IL-10） , myeloperoxidase of lung were studied at 45 min after pulmonary ischemia and 60,120 min of reperfusion. The cell counts, percentage of PMN, the lung permeability index and light and electron microscopic examination in left bronchoalveolar lavage fluid（BALF） were performed at 120 of reperfusion. Results During reperfusion ,The lung W/D , the levels of TNFα and IL-1 β and myeloperoxidase in group IR and group Sev -IR were increased progressively and significantly higher than those in group S , but compared with group IR , pre-administration of sevoflurane could inhibite the increases of index above-mentioned after 120 min of reperfusion（ P 〈 0.05 ）. Lung permeability index significantly increased in group IR and Sev-IR more than that in group S at 120 rain of reperfusion（ P 〈 0.01 ）, but the degree of increase in lung permeability index of group Sev-IR was decreased markedly compared with of group IR （P 〈 0.05 ）. IL-10 content of lung significantly decreased in group IR and group Sev -IR than that in group S, but the IL-10 content of group Sev-IR was increased markedly compared with that of group IR. Histological examination showed that the IR induced lung injury was also ameliorated by sevoflurane pretreatment. Conclusion Inhalation of sevoflurane before isehemia could protect the lung against IR injury in rabbits through an inhibition of PMN infiltration and the release of TNFα and L-1 β, and an increase in the expression of IL-10.