The Effect and Mechanism of Pentoxifylline Pretreatment on Aucte Lung Injury Induced by Unresuscitated Hemorrhagic Shock_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LV Tangfeng , SONG Yong , SHI Yi , LI Ziling , XIN Xiaofeng

Department of Respiratory Diseases, Nanjing General Hospital of Nanjing Command, Nanjing University Clinical School of Medicine. Nanjing, Jiangsu, 210002, ChinaCorresponding Author: SONG Yong, E-mail: yong_song6310@ yahoo. com;

Corresponding author：

Keywords：

Acute lung injury; Hemorrhagic shock; Pentoxifylline; Toll like receptor 4

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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 TNF-αand IL-1βin 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( P lt; 0. 01) . The expressions of TNF-α, IL-1β, TLR4 mRNA and TLR4 protein were also significantly higher than the control group( P lt;0. 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 mechanismmay relate to down-regulation of TLR4, thus inhibit the expression of pro-inflammatory cytokins.

Citation： LV Tangfeng,SONG Yong,SHI Yi,LI Ziling,XIN Xiaofeng. The Effect and Mechanism of Pentoxifylline Pretreatment on Aucte Lung Injury Induced by Unresuscitated Hemorrhagic Shock. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(6): 619-623. doi: Copy

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6.	de Campos T, Deree J, Martins JO, et al. Pentoxifylline attenuates pulmonary inflammation and neutrophil activation in experimental acute pancreatitis. Pancreas, 2008 , 37: 42-49.
7.	Song 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.
8.	Aderem 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, 等. 失血性休克后小鼠肺组织TLR4 受体表达及其意义. 中国呼吸与危重监护杂志, 2005 , 4: 435-437 .
10.	Chen C,Wang Y, Zhang Z, et al. Toll-like receptor 4 regulates heme 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.
11.	Sato H, Tanaka T, Kita T, et al. A quantitative study of lung dysfunction following haemorrhagic shock in rats. Int J Exp Pathol,2010, 91: 267-275 .

1. Fan J. TLR4 cross-talk mechanism of hemorrhagic shock-primed pulmonary neutrophil infiltraction. Open Crit Care Med J,2010,2:1-8.
2. Liu 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.
3. Huang HL, Lin CW, Chiang MF, et al. Lipopolysaccharide 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 cells. J Cell Biochem,2010, Jul 21, [ Epub ahead of print] .
4. Lv 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.
5. Fan 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 .
6. de Campos T, Deree J, Martins JO, et al. Pentoxifylline attenuates pulmonary inflammation and neutrophil activation in experimental acute pancreatitis. Pancreas, 2008 , 37: 42-49.
7. Song 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.
8. Aderem 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, 等. 失血性休克后小鼠肺组织TLR4 受体表达及其意义. 中国呼吸与危重监护杂志, 2005 , 4: 435-437 .
10. Chen C,Wang Y, Zhang Z, et al. Toll-like receptor 4 regulates heme 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.
11. Sato H, Tanaka T, Kita T, et al. A quantitative study of lung dysfunction following haemorrhagic shock in rats. Int J Exp Pathol,2010, 91: 267-275 .

Chinese Journal of Respiratory and Critical Care Medicine

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

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