• 1 第三軍醫(yī)大學(xué)附屬新橋醫(yī)院呼吸病研究所(重慶 400037);;
  • 2 東南大學(xué)中大醫(yī)院呼吸科;

目的   研究脂多糖結(jié)合蛋白(LBP)抑制肽P12對脂多糖(LPS)與小鼠肺泡巨噬細(xì)胞(AMs)結(jié)合的抑制作用,探討LBP抑制肽體內(nèi)阻斷內(nèi)毒素信號傳導(dǎo)通路的機(jī)制。方法  40只小鼠隨機(jī)分為5組:對照組、內(nèi)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(nèi)注射LPS復(fù)制內(nèi)毒素血癥模型,尾靜脈注射P12,流式細(xì)胞檢測分析(FACS)異硫氰酸熒光素標(biāo)記的LPS(FITC-LPS)與AMs的結(jié)合,以平均熒光強(qiáng)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(jié)果  內(nèi)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(nèi)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(nèi)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(nèi)毒素血癥組(P均 lt;0.05)。結(jié)論  LBP抑制肽P12抑制了LPS與內(nèi)毒素血癥小鼠AMs的結(jié)合,顯著降低了LPS誘導(dǎo)的TNF-α的產(chǎn)生。

引用本文: 吳學(xué)玲 ,趙云峰,錢桂生,徐德彬,陳維中. 脂多糖結(jié)合蛋白抑制肽對脂多糖與內(nèi)毒素血癥小鼠肺泡巨噬細(xì)胞結(jié)合的影響. 中國呼吸與危重監(jiān)護(hù)雜志, 2008, 08(3): 195-198. doi: 復(fù)制

1. 王興鵬,吳麗穎,吳愷,等.脂多糖結(jié)合蛋白在實(shí)驗(yàn)性急性壞死型胰腺炎發(fā)生中的作用.中華醫(yī)學(xué)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(jié)合蛋白功能位點(diǎn)分析.解放軍醫(yī)學(xué)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(jié)合蛋白抗炎功能位點(diǎn)的研究.第三軍醫(yī)大學(xué)學(xué)報(bào),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(xué)玲,錢桂生,徐德斌,等.肺損傷機(jī)制研究:脂多糖結(jié)合蛋白抑制肽對脂多糖誘導(dǎo)的人單核細(xì)胞株核轉(zhuǎn)錄因子κB活性的影響.中國臨床康復(fù),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(xué)玲,錢桂生,趙云峰,等.脂多糖結(jié)合蛋白抑制肽抑制脂多糖與人單核巨噬細(xì)胞株的結(jié)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(xué)玲,錢桂生,徐德斌,等.脂多糖結(jié)合蛋白抑制肽對內(nèi)毒素誘導(dǎo)的U937細(xì)胞TLR4的影響.中國急救醫(yī)學(xué),2005,25:46-47.
15. 吳學(xué)玲,錢桂生,徐德斌,等.脂多糖結(jié)合蛋白抑制肽對內(nèi)毒素誘導(dǎo)的人單核巨噬細(xì)胞株表達(dá)CD14的影響.中國呼吸與危重監(jiān)護(hù)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.
  1. 1. 王興鵬,吳麗穎,吳愷,等.脂多糖結(jié)合蛋白在實(shí)驗(yàn)性急性壞死型胰腺炎發(fā)生中的作用.中華醫(yī)學(xué)雜志,2003,83:1619-1623.
  2. 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. 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. 4. 徐德斌,錢桂生,侯一峰,等.脂多糖結(jié)合蛋白功能位點(diǎn)分析.解放軍醫(yī)學(xué)雜志,2004,29:85.
  5. 5. 徐德斌,錢桂生,侯一峰,等.噬菌體展示短肽模擬脂多糖結(jié)合蛋白抗炎功能位點(diǎn)的研究.第三軍醫(yī)大學(xué)學(xué)報(bào),2004,26:573-575.
  6. 6. Wu XL,Qian GS.Effect of LBP inhibitory peptide on U937 cells exposed to LPS.Respirology,2004,9(suppl):A164.
  7. 7. 吳學(xué)玲,錢桂生,徐德斌,等.肺損傷機(jī)制研究:脂多糖結(jié)合蛋白抑制肽對脂多糖誘導(dǎo)的人單核細(xì)胞株核轉(zhuǎn)錄因子κB活性的影響.中國臨床康復(fù),2005,9:89-91.
  8. 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. 9. Polderman KH,Girbes AR.Drug intervention trials in sepsis:divergent results.Lancet,2004,363:1721-1723.
  10. 10. Chaby R.Strategies for the control of LPS-mediated pathophysiological disorders.Drug Discovery Today,1999,4:209-221.
  11. 11. 吳學(xué)玲,錢桂生,趙云峰,等.脂多糖結(jié)合蛋白抑制肽抑制脂多糖與人單核巨噬細(xì)胞株的結(jié)合.中國病理生理雜志,2007,23:1392-1395.
  12. 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. 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. 14. 吳學(xué)玲,錢桂生,徐德斌,等.脂多糖結(jié)合蛋白抑制肽對內(nèi)毒素誘導(dǎo)的U937細(xì)胞TLR4的影響.中國急救醫(yī)學(xué),2005,25:46-47.
  15. 15. 吳學(xué)玲,錢桂生,徐德斌,等.脂多糖結(jié)合蛋白抑制肽對內(nèi)毒素誘導(dǎo)的人單核巨噬細(xì)胞株表達(dá)CD14的影響.中國呼吸與危重監(jiān)護(hù)雜志,2005,4:230-232.
  16. 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.
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