地氟烷预处理对脂多糖所致肺损伤幼年大鼠的影响

Effect of pretreatment with desflurane on lipopolysaccharide-induced lung injury in juvenile rats

目的 探讨地氟烷预处理对脂多糖所致肺损伤幼年大鼠的影响及其机制。方法 将60只18日龄Wistar大鼠随机分为对照组(C组)、脂多糖组(L组)、1.0最大允许浓度(MAC)地氟烷组(D1.0组)和1.5MAC地氟烷组(D1.5组),每组15只。除C组外,其他3组建立脂多糖诱导肺损伤模型,D1.0组和D1.5组大鼠建模前分别吸入1.0MAC和1.5MAC地氟烷40min。建模后8h,计算肺组织湿/干比评估肺水肿程度,镜下观察肺组织损伤情况,检测血清和肺泡灌洗液白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)水平,分析肺组织活性氧簇(ROS)阳性率和线粒体膜电位(MMP)的耗散,并检测CXC受体(CXCR)1、CXCR2和CD11bmRNA和蛋白的表达水平。结果 与C组比较,L组、D1.0组和D1.5组大鼠肺组织湿/干比、病理学评分、ROS阳性率和MMP耗散增加(均P<0.05),而D1.0组和D1.5组以上指标均低于L组(均P<0.05)。L组、D1.0组和D1.5组大鼠血清和肺泡灌洗液IL-1β和TNF-α水平,以及CXCR1、CXCR2和CD11bmRNA和蛋白表达水平均高于C组,而D1.0组和D1.5组以上指标水平均低于L组(均P<0.05)。D1.0组和D1.5组间所有指标比较,差异均无统计学意义(均P>0.05)。结论 地氟烷预处理可减轻脂多糖所致幼年大鼠肺损伤,其机制可能是通过干扰CXCR2信号通路减少ROS生成和MMP的耗散。

Objective To explore the effect and mechanism of pretreatment with desflurane on lipopolysaccharide-induced lung injury in juvenile rats.Methods Sixty Wistar rats aged 18 days were randomly divided into control group(group C),lipopolysaccharide group(group L),1.0 maximum allowable concentration(MAC)desflurane group(group D 1.0)and 1.5 MAC desflurane group(group D 1.5),with 15 rats in each group.Except group C,the model of lipopolysaccharide-induced lung injury was established in the other three groups,and inhalation of 1.0 MAC and 1.5 MAC desflurane was performed in the rats of group D 1.0 and group D 1.5 before modeling,respectively.Eight hours after modeling,the wet-to-dry weight ratio of lung tissue was calculated to assess the severity of pneumonedema,the condition of lung injury was observed under microscope,the levels of interleukin(IL)-1βand tumor necrosis factorα(TNF-α)in serum and bronchoalveolar lavage fluid(BALF)were detected,the positive rate of reactive oxygen species(ROS)and consumption of mitochondrial membrane potential(MMP)in lung tissues were analyzed,and the protein and mRNA expression levels of CXC receptor(CXCR)1,CXCR2 and CD11b were also determined.Results Compared with group C,rats in group L,group D 1.0 and group D 1.5 had increased wet-to-dry weight ratio,pathological score,ROS positive rate,and MMP consumption(all P<0.05),and the indices above in group D 1.0 and group D 1.5 were lower than those in group L(all P<0.05).Rats in group L,group D 1.0 and group D 1.5 had higher serum and BALF IL-1βand TNF-αlevels,and higher mRNA and protein expression levels of CXCR1,CXCR2,and CD11b than group C,and the indices above in group D 1.0 and group D 1.5 were lower than those in group L(all P<0.05).There were no statistically significant differences in all of the indices between group D 1.0 and group D 1.5(all P>0.05).Conclusion Pretreatment with desflurane can attenuate lipopolysaccharide-induced lung injury in juvenile rats,and its potential mechanism is associated with decline in ROS production and MMP consumption through interfering CXCR2 signaling pathway.