目的 研究脂多糖結合蛋白(LBP)抑制肽P12對脂多糖(LPS)與小鼠肺泡巨噬細胞(AMs)結合的抑制作用,探討LBP抑制肽體內阻斷內毒素信號傳導通路的機制。方法 40只小鼠隨機分為5組:對照組、內毒素血癥組、低劑量P12組、中劑量P12組和高劑量P12組,每組8只。腹腔內注射LPS復制內毒素血癥模型,尾靜脈注射P12,流式細胞檢測分析(FACS)異硫氰酸熒光素標記的LPS(FITC-LPS)與AMs的結合,以平均熒光強度(MFI)表示;ELISA法檢測小鼠血清中腫瘤壞死因子α(TNF-α)的含量。結果 內毒素血癥組小鼠AMs MFI明顯高于對照組(45.31%比4.61%,P lt;0.05);低劑量P12組、中劑量P12組和高劑量P12組的MFI分別為40.08%、30.76%和24.45%,明顯低于內毒素血癥組(低劑量組P>0.05,中劑量P12組和高劑量組P均 lt;0.05)。內毒素血癥組小鼠血清中TNF-α的含量顯著高于對照組[(180.17±39.14)pg/mL比(24.88±5.82)pg/mL,P lt;0.01];低劑量P12組、中劑量P12組和高劑量P12組血清中TNF-α的含量分別為(112.69±19.78)pg/mL、(86.34±9.25)和(70.48±8.48)pg/mL,均明顯低于內毒素血癥組(P均 lt;0.05)。結論 LBP抑制肽P12抑制了LPS與內毒素血癥小鼠AMs的結合,顯著降低了LPS誘導的TNF-α的產生。
引用本文:
吳學玲 ,趙云峰,錢桂生,徐德彬,陳維中. 脂多糖結合蛋白抑制肽對脂多糖與內毒素血癥小鼠肺泡巨噬細胞結合的影響. 中國呼吸與危重監護雜志, 2008, 08(3): 195-198. doi:
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Wu X,Qian G,Zhao Y,et al.LBP inhibitory peptide reduces endotoxin-induced macrophage activation and mortality.Inflamm Res,2005,54:451-457.
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- 1. 王興鵬,吳麗穎,吳愷,等.脂多糖結合蛋白在實驗性急性壞死型胰腺炎發生中的作用.中華醫學雜志,2003,83:1619-1623.
- 2. Dentener MA,Vreugdenhil AC,Hoet PH,et al.Production of the acute-phase protein lipopolysaccharide-binding protein by respiratory type II epithelial cells:implications for local defense to bacterial endotoxins.Am J Respir Cell Mol Biol,2000,23:146-153.
- 3. Le Roy D,Di Padova F,Tees R,et al.Monoclonal antibodies to murine lipopolysaccharide (LPS)-binding protein (LBP) protect mice from lethal endotoxemia by blocking either the binding of LPS to LBP or the presentation of LPS/LBP complexes to CD14.J Immunol,1999,162:7454-7460.
- 4. 徐德斌,錢桂生,侯一峰,等.脂多糖結合蛋白功能位點分析.解放軍醫學雜志,2004,29:85.
- 5. 徐德斌,錢桂生,侯一峰,等.噬菌體展示短肽模擬脂多糖結合蛋白抗炎功能位點的研究.第三軍醫大學學報,2004,26:573-575.
- 6. Wu XL,Qian GS.Effect of LBP inhibitory peptide on U937 cells exposed to LPS.Respirology,2004,9(suppl):A164.
- 7. 吳學玲,錢桂生,徐德斌,等.肺損傷機制研究:脂多糖結合蛋白抑制肽對脂多糖誘導的人單核細胞株核轉錄因子κB活性的影響.中國臨床康復,2005,9:89-91.
- 8. Knapp S,Wieland CW,van ’t Veer C,et al.Toll-like receptor 2 plays a role in the early inflammatory response to murine pneumococcal pneumonia but does not contribute to antibacterial defense.J Immunol,2004,172:3132-3138.
- 9. Polderman KH,Girbes AR.Drug intervention trials in sepsis:divergent results.Lancet,2004,363:1721-1723.
- 10. Chaby R.Strategies for the control of LPS-mediated pathophysiological disorders.Drug Discovery Today,1999,4:209-221.
- 11. 吳學玲,錢桂生,趙云峰,等.脂多糖結合蛋白抑制肽抑制脂多糖與人單核巨噬細胞株的結合.中國病理生理雜志,2007,23:1392-1395.
- 12. Hamada M,Yamamoto S,Moriguchi S,et al.Phagocytosis of alveolar macrophages after conagenin injection to rats.J Antibiot,2001,54:349-353.
- 13. Le Roy D,Di Padova F,Adachi Y,et al.Critical role of lipopolysaccharide-binding protein and CD14 in immune responses against gram-negative bacteria.J Immunol,2001;167:2759-2765.
- 14. 吳學玲,錢桂生,徐德斌,等.脂多糖結合蛋白抑制肽對內毒素誘導的U937細胞TLR4的影響.中國急救醫學,2005,25:46-47.
- 15. 吳學玲,錢桂生,徐德斌,等.脂多糖結合蛋白抑制肽對內毒素誘導的人單核巨噬細胞株表達CD14的影響.中國呼吸與危重監護雜志,2005,4:230-232.
- 16. Wu X,Qian G,Zhao Y,et al.LBP inhibitory peptide reduces endotoxin-induced macrophage activation and mortality.Inflamm Res,2005,54:451-457.