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  

The Effect and Mechanism of Pentoxifylline Pretreatment on Aucte Lung Injury Induced by Unresuscitated Hemorrhagic Shock

作　　者：吕镗烽[1] 宋勇[1] 施毅[1] 李子玲[1] 辛晓峰[1] 

机构地区：[1]南京军区南京总医院呼吸科,江苏南京210002

出　　处：《中国呼吸与危重监护杂志》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)

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.

关 键 词：急性肺损伤 失血性休克 己酮可可碱 TOLL样受体4 

分 类 号：R459.7[医药卫生—急诊医学] R563.8[医药卫生—治疗学]