目的 觀察給予己酮可可堿( PTX) 預處理對失血性休克致急性肺損傷( ALI) 小鼠的影響, 初步探討PTX 的作用機制。方法 小鼠分為對照組、失血性休克組及PTX 組。通過肺組織HE染色觀察病理改變, 同時檢測肺干濕比( W/D) 和髓過氧化物酶( MPO) 活性。通過ELISA 方法檢測肺組織腫瘤壞死因子α( TNF-α) 和IL-1β變化, 通過逆轉錄-聚合酶鏈反應( RT-PCR) 檢測肺組織Toll 樣受體4( TLR4) mRNA 的表達, 通過Western blot 檢測肺組織TLR4 蛋白的變化。結果 失血性休克誘導小鼠產生ALI, 肺W/D 和MPO 活性明顯增加, TNF-α、IL-1β、TLR4 mRNA 和TLR4 蛋白表達也增高, 與對照組有顯著性差異( P lt; 0. 01) 。PTX 預處理能減輕失血性休克所致ALI, 降低肺W/D 和MPO 活性, 同時導致TNF-α、IL-1β、TLR4 mRNA 和TLR4 蛋白表達下降。結論 PTX 預處理對失血性休克所致ALI 起保護作用, 可能與通過下調TLR4 抑制促炎癥因子表達有關。
引用本文： 呂鏜烽,宋勇,施毅,李子玲,辛曉峰. 己酮可可堿預處理對單純性失血性休克致小鼠急性肺損傷的影響及其機制. 中國呼吸與危重監(jiān)護雜志, 2010, 9(6): 619-623. doi: 復制
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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 受體表達及其意義. 中國呼吸與危重監(jiān)護雜志, 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 .