目的 觀察給予己酮可可堿( PTX) 預(yù)處理對(duì)失血性休克致急性肺損傷( ALI) 小鼠的影響, 初步探討PTX 的作用機(jī)制。方法 小鼠分為對(duì)照組、失血性休克組及PTX 組。通過肺組織HE染色觀察病理改變, 同時(shí)檢測(cè)肺干濕比( W/D) 和髓過氧化物酶( MPO) 活性。通過ELISA 方法檢測(cè)肺組織腫瘤壞死因子α( TNF-α) 和IL-1β變化, 通過逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)( RT-PCR) 檢測(cè)肺組織Toll 樣受體4( TLR4) mRNA 的表達(dá), 通過Western blot 檢測(cè)肺組織TLR4 蛋白的變化。結(jié)果 失血性休克誘導(dǎo)小鼠產(chǎn)生ALI, 肺W/D 和MPO 活性明顯增加, TNF-α、IL-1β、TLR4 mRNA 和TLR4 蛋白表達(dá)也增高, 與對(duì)照組有顯著性差異( P lt; 0. 01) 。PTX 預(yù)處理能減輕失血性休克所致ALI, 降低肺W/D 和MPO 活性, 同時(shí)導(dǎo)致TNF-α、IL-1β、TLR4 mRNA 和TLR4 蛋白表達(dá)下降。結(jié)論 PTX 預(yù)處理對(duì)失血性休克所致ALI 起保護(hù)作用, 可能與通過下調(diào)TLR4 抑制促炎癥因子表達(dá)有關(guān)。
引用本文： 呂鏜烽,宋勇,施毅,李子玲,辛?xí)苑? 己酮可可堿預(yù)處理對(duì)單純性失血性休克致小鼠急性肺損傷的影響及其機(jī)制. 中國呼吸與危重監(jiān)護(hù)雜志, 2010, 9(6): 619-623. doi: 復(fù)制
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- 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. 呂鏜烽, 宋勇, 施毅, 等. 失血性休克后小鼠肺組織TLR4 受體表達(dá)及其意義. 中國呼吸與危重監(jiān)護(hù)雜志, 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 .