地氟烷预处理对脂多糖所致肺损伤幼年大鼠的影响
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摘要
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(D_(1. 0)组)和1. 5MAC地氟烷组(D_(1. 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,D_(1. 0)组和D_(1. 5)组大鼠建模前分别吸入1. 0 MAC和1. 5 MAC地氟烷40 min。建模后8 h,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CD11b mRNA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D_(1. 0)组和D_(1. 5)组以上指标均低于L组(均P <0. 05)。L组、D_(1. 0)组和D_(1. 5)组大鼠血清和肺泡灌洗液IL-1β和TNF-α水平,以及CXCR1、CXCR2和CD11b mRNA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)。D_(1. 0)组和D_(1. 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 and1. 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)-1β and tumor necrosis factor α( 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 CD11 b 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-1β and TNF-α levels,and higher mRNA and protein expression levels of CXCR1,CXCR2,and CD11 b 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.
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 and1. 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)-1β and tumor necrosis factor α( 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 CD11 b 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-1β and TNF-α levels,and higher mRNA and protein expression levels of CXCR1,CXCR2,and CD11 b 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.
引文
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[11] Madl AK,Plummer LE,Carosino C,et al. Nanoparticles,lung injury,and the role of oxidant stress[J]. Annu Rev Physiol,2014,76:447-465.
[12] Iijima T. Mitochondrial membrane potential and ischemic neuronal death[J]. Neurosci Res,2006,55(3):234-243.
[13] Cao Q,Li B,Wang X,et al. Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice[J]. Arch Med Sci,2018,14(3):635-644.
[14] Ha H,Debnath B,Odde S,et al. Discovery of novel CXCR2inhibitors using ligand-based pharmacophore models[J]. J Chem Inf Model,2015,55(8):1 720-1 738.
[15] Aziz M,Matsuda A,Yang WL,et al. Milk fat globule-epidermal growth factor-factor 8 attenuates neutrophil infiltration in acute lung injury via modulation of CXCR2[J]. J Immunol,2012,189(1):393-402.
[2] Mercier FJ,Naline E,Bardou M,et al. Relaxation of proximal and distal isolated human bronchi by halothane,isoflurane and desflurane[J]. Eur Respir J,2002,20(2):286-292.
[3] Tsai SK,Lin SM,Hung WC,et al. The effect of desflurane on ameliorating cerebral infarction in rats subjected to focal cerebral ischemia-reperfusion injury[J]. Life Sci,2004,74(20):2 541-2 549.
[4]张兵,魏霞,李文志,等.地氟烷预先给药对大鼠前脑缺血再灌注时线粒体通透性转换孔和膜电位的影响[J].中华麻醉学杂志,2008,28(2):171-174.
[5]张兵,魏霞,李文志,等.地氟烷对大鼠脑缺血再灌注时线粒体呼吸链复合体活性的影响[J].中华麻醉学杂志,2008,28(4):365-368.
[6] Müller-Edenborn B,Frick R,Piegeler T,et al. Volatile anaesthetics reduce neutrophil inflammatory response by interfering with CXC receptor-2 signalling[J]. Br J Anaesth,2015,114(1):143-149.
[7]宋潇,王凯,王立伟,等.富氢液对大鼠内毒素性急性肺损伤时TLR4/MyD88信号通路的影响[J].中华麻醉学杂志,2016,36(1):120-122.
[8]荆忍,潘灵辉.线粒体自噬在大鼠VILI中的作用及机制[J].中华危重病急救医学,2017,29(1):6-10.
[9] Oberkampf M,Guillerey C,Mouriès J,et al. Mitochondrial reactive oxygen species regulate the induction of CD8+T cells by plasmacytoid dendritic cells[J]. Nat Commun,2018,9(1):2 241.
[10] Chow CW,Herrera Abreu MT,Suzuki T,et al. Oxidative stress and acute lung injury[J]. Am J Respir Cell Mol Biol,2003,29(4):427-431.
[11] Madl AK,Plummer LE,Carosino C,et al. Nanoparticles,lung injury,and the role of oxidant stress[J]. Annu Rev Physiol,2014,76:447-465.
[12] Iijima T. Mitochondrial membrane potential and ischemic neuronal death[J]. Neurosci Res,2006,55(3):234-243.
[13] Cao Q,Li B,Wang X,et al. Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice[J]. Arch Med Sci,2018,14(3):635-644.
[14] Ha H,Debnath B,Odde S,et al. Discovery of novel CXCR2inhibitors using ligand-based pharmacophore models[J]. J Chem Inf Model,2015,55(8):1 720-1 738.
[15] Aziz M,Matsuda A,Yang WL,et al. Milk fat globule-epidermal growth factor-factor 8 attenuates neutrophil infiltration in acute lung injury via modulation of CXCR2[J]. J Immunol,2012,189(1):393-402.