期刊文献+

己酮可可碱预处理对单纯性失血性休克致小鼠急性肺损伤的影响及其机制 被引量:1

The Effect and Mechanism of Pentoxifylline Pretreatment on Aucte Lung Injury Induced by Unresuscitated Hemorrhagic Shock
暂未订购
导出
摘要 目的观察给予己酮可可碱(PTX)预处理对失血性休克致急性肺损伤(ALI)小鼠的影响,初步探讨PTX的作用机制。方法小鼠分为对照组、失血性休克组及PTX组。通过肺组织HE染色观察病理改变,同时检测肺干湿比(W/D)和髓过氧化物酶(MPO)活性。通过ELISA方法检测肺组织肿瘤坏死因子α(TNF-α)和IL-1β变化,通过逆转录-聚合酶链反应(RT-PCR)检测肺组织Toll样受体4(TLR4)mRNA的表达,通过Western blot检测肺组织TLR4蛋白的变化。结果失血性休克诱导小鼠产生ALI,肺W/D和MPO活性明显增加,TNF-α、IL-1β、TLR4 mRNA和TLR4蛋白表达也增高,与对照组有显著性差异(P<0.01)。PTX预处理能减轻失血性休克所致ALI,降低肺W/D和MPO活性,同时导致TNF-α、IL-1β、TLR4 mRNA和TLR4蛋白表达下降。结论 PTX预处理对失血性休克所致ALI起保护作用,可能与通过下调TLR4抑制促炎症因子表达有关。 Objective To investigate the effects and mechanisms of pentoxifylline(PTX) pretreatment on acute lung injury(ALI) induced by hemorrhagic shock in mice.Methods Ninety mice were randomly divided into three groups,ie.a control group,a hemorrhagic shock group,and a PTX group.Lung histological changes were examined by HE staining.Meanwhile,the wet-to-dry weight ratio(W/D) and myeloperoxidase(MPO) activity in lung were measured.The levels of TNFα and IL-1β in lung homogenate were measured by ELISA.The expressions of TLR4 mRNA and TLR4 protein in lung were detected by reverse transcription-polymerase chain reaction(RT-PCR) and Western blot,respectively.Results Hemorrhagic shock induced obvious ALI changes in lungs of the hemorrhagic shock group.W/D and MPO activity were significantly higher in the hemorrhagic shock group than the control group(P0.01).The expressions of TNF-α,IL-1β,TLR4 mRNA and TLR4 protein were also significantly higher than the control group(P0.01).PTX pretreatment could relieve ALI changes induced by hemorrhagic shock,and decrease W/D and MPO activity.The expressions of TNF-α,IL-1β,TLR4 mRNA and TLR4 protein were also decreased by PTX pretreatment.Conclusions PTX pretreatment shows protective effects on ALI after hemorrhagic shock.Its possible mechanism may relate to down-regulation of TLR4,thus inhibit the expression of pro-inflammatory cytokins.
出处 《中国呼吸与危重监护杂志》 CAS 2010年第6期619-623,共5页 Chinese Journal of Respiratory and Critical Care Medicine
基金 国家青年自然科学基金(编号:30900649/H0111)
关键词 急性肺损伤 失血性休克 己酮可可碱 TOLL样受体4 Acute lung injury Hemorrhagic shock Pentoxifylline Toll like receptor 4
  • 相关文献

参考文献11

  • 1Fan J. TLR4 cross-talk mechanism of hemorrhagic shock-primed pulmonary neutrophil infiltraction. Open Crit Care Med J ,2010,2:1-8.
  • 2Liu Y, Yuan Y, Li Y, et al. Interacting neuroendocrine and innate and acquired immune pathways regulate neutrophil mobilization from bone marrow following hemorrhagic shock. J Immunol, 2009,182 : 572-580.
  • 3Huang HL, Lin CW, Chiang MF, et al. IJpopolysaccharide directly stimulates aldosterone production via toll-like receptor 2 and toll-like receptor 4 related PI(3)K/Akt pathway in rat adrenal zona glomerulosa ceils. J Cell Biochem,2010,Jul 21, [ Epub ahead of print].
  • 4Lv T, Shen X, Shi Y, et al. TLR4 is essential in acute lung injury induced by unresuscitated hemorrhagic shock. J trauma,2009,66, 124-131.
  • 5Fan J,Li Y,Levy RM,et al. Hemorrhagic shock induces NAD(P) H oxidase activation in neutrophils:role of HMGB1-TLR4 signaling. J Immunol,2007 ,178 :6573-6580.
  • 6de Campos T, Deree J, Martins JO, et al. Pentoxifylline attenuates pulmonary inflammation and neutrophil activation in experimental acute panereatitis. Pancreas, 2008,37 : 42 -49.
  • 7Song Y, Ao L, Calkins CM, et al. Differential cardiopulmonary recruitment of neutrophils during hemorrhagic shock: a role for ICAM-1 ? Shock ,2001,16:444-448.
  • 8Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature, 2000,406 : 782 -787.
  • 9吕镗烽,宋勇,施毅,印洪林.失血性休克后小鼠肺组织TLR4受体表达及其意义[J].中国呼吸与危重监护杂志,2005,4(6):435-437. 被引量:1
  • 10Chen C,Wang Y,Zhang Z,et al. Toll-like receptor 4 regulates heine oxygenase-1 expression after hemorrhagic shock induced acute lung injury in mice : requirement of p38 mitogen-activated protein kinase activation. Shock ,2009,31:486-492.

二级参考文献12

  • 1张静,瞿介明,潘珏,何礼贤,欧周罗,张杏怡,陈雪华.内毒素耐受大鼠与正常大鼠急性肺损伤反应比较[J].中国呼吸与危重监护杂志,2003,2(6):346-350. 被引量:11
  • 2Medvedev AE,Vogel SN.Overexpression of CD14,TLR4,and MD-2 in HEK 293T cells does not prevent induction of in vitro endotoxin tolerance.J Endotoxin Res,2003;9:60-64.
  • 3Takeuchi O,Hoshino K,Kawai T,et al.Defferential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components.Immunity,1999;11:443-451.
  • 4Williams DL,Ha T,Li C,et al.Modulation of tissue Toll-like receptor 2 and 4 during the early phases of polymicrobial sepsis correlates with mortality.Crit Care Med,2003;31:1808-1818.
  • 5Qureshi ST,Lariviere L,Leveque G,et al.Endotoxin-tolerant mice have mutations in Toll-like receptor 4(Tlr4).J Exp Med,1999;189:615-625.
  • 6Song Y,Ao L,Calkins CM,et al.Differential cardiopulmonary recruitment of neutrophils during hemorrhagic shock:a role for ICAM-1? Shock,2001;16:444-448.
  • 7Fan J,Kapus A,Marsden PA,et al.Regulation of Toll-like receptor 4 expression in the lung following hemorrhagic shock and lipopolysaccharide.J Immunol,2002;168:5252-5259.
  • 8Calkins CM,Heimbach JK,Bensard DD,et al.TNF receptor Ⅰ mediates chemokine production and neutrophil accumulation in the lung following systemic lipopolysaccharide.J Surg Res,2001;101:232-237.
  • 9Barsness KA,Arcaroli J,Harken AH,et al.Hemorrhage-induced acute lung injury is TLR-4 dependent.Am J Physiol Regul Integr Comp Physiol,2004;287:R592-R599.
  • 10Sherwood ER.Current concepts of the inflammatory response.ASA Refr Courses Anesthesiol,2002;30:169-184.

同被引文献17

  • 1Alam HB,Rhee P.New developments in fluid resuscitation[J].Surg Clin North Am,2007,87(1):55-72.
  • 2Lee WL,Downey GP.Neutrophil activation and acute lung injury[J].Curr Opin Crit Care,2001,7(1):1-7.
  • 3Fan J.TLR cross-talk mechanism of hemorrhagic shock-primed pulmonary neutrophil infiltration[J].Open Crit Care Med J,2010(2):1-8.
  • 4Liu Y,Yuan Y,Li Y,et al.Interacting neuroendocrine and innate and acquired immune pathways regulate neutrophil mobilization from bone marrow following hemorrhagic shock[J].J Immunol,2009,182(1):572-580.
  • 5Alam HB,Sun L,Ruff P,et al.E-and P-selectin expression depends on the resuscitation fluid used in hemorrhaged rats[J].J Surg Res,2000,94(2):145-152.
  • 6Alam HB,Santon K,Koustova E,et al.Effects of different resuscitation strategies on neutrophil activation in a swine model of hemorrhagic shock[J].Resuscitation,2004,60(1):91-99.
  • 7Savage SA,Fitzpatrick CM,Kashyap VS,et al.Endothelial dysfunction after lactated Ringer's solution resuscitation for hemorrhagic shock[J].J Trauma,2005,59(2):284-290.
  • 8Deree J,de Campos T,Shenvi E,et al.Hypertonic saline and pentoxifylline attenuates gut injury after hemorrhagic shock:the kinder,gentler resuscitation[J].J Trauma,2007,62(4):818-828.
  • 9Deree J,Martins J,de Campos T,et al.Pentoxifylline attenuates lung injury and modulates transcription factor activity in hemorrhagic shock[J].J Surg Res,2007,143(1):99-108.
  • 10Lomas-Niera JL,Perl M,Chunq CS,et al.Sock and hemorrhagic:an overview of animal models[J].Shock,2005,24 Suppl 1:33-39.

引证文献1

二级引证文献2

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部