• 1. 昆明醫(yī)學(xué)院第一附屬醫(yī)院胃腸與甲狀腺外科(云南昆明 650032);;
  • 2. 昆明市第一人民醫(yī)院暨昆明醫(yī)學(xué)院附屬甘美醫(yī)院器官移植中心(云南昆明 650011);

目的  建立腹腔注射穿孔性腹膜炎腹水(PPAF)誘導(dǎo)大鼠急性肺損傷(ALI)模型,探討ALI的發(fā)生機(jī)理和L-精氨酸(L-Arg)的作用。
方法  60只SD大鼠建立消化道穿孔性腹膜炎(PP)模型,收集PPAF;48只大鼠按隨機(jī)數(shù)字表法分為NS組(n=16),PPAF組(n=16)和L-Arg組(n=16)。各組大鼠再按隨機(jī)數(shù)字表法分為7h和12h2個(gè)亞組。檢測外周血WBC計(jì)數(shù)、血清NO及脂質(zhì)過氧化物丙二醛(MDA)水平、肺組織病理損害評分、肺組織濕/干質(zhì)量比、肺組織髓過氧化物酶(MPO)水平和肺細(xì)胞凋亡情況。
結(jié)果  PPAF組各時(shí)間點(diǎn)血WBC計(jì)數(shù)、血清NO及MDA水平、肺組織MPO水平、肺組織病理損害評分、濕/干質(zhì)量比和細(xì)胞凋亡率均高于NS組(P<0.01)。L-Arg組血清NO水平顯著高于PPAF組(P<0.01),血清MDA水平、肺組織MPO水平、肺組織病理損害評分和濕/干質(zhì)量比以及細(xì)胞凋亡率均顯著低于PPAF組(P<0.05)。PPAF組和L-Arg組12h血清NO水平、肺濕/干質(zhì)量比和細(xì)胞凋亡率均顯著高于7h(P=0.000)。PPAF組和L-Arg組血清NO水平與血清MDA水平(r=-0.257,P=0.021)、肺組織MPO水平(r=-0.444, P=0.011)和肺細(xì)胞凋亡率(r=-0.351,P=0.010)呈負(fù)相關(guān)。各組血清MDA與肺細(xì)胞凋亡率呈正相關(guān)(r = 0.969,P<0.001)。
結(jié)論  腹腔注射PPAF可誘導(dǎo)大鼠ALI,肺內(nèi)氧化反應(yīng)增強(qiáng)和細(xì)胞凋亡參與了ALI的發(fā)生,而L-Arg對ALI具有保護(hù)作用。

引用本文: 蘇艷軍,劉其雨,刁暢,張建明,李立,程若川. L-Arg 與腹腔注射PPAF 誘導(dǎo)的大鼠急性肺損傷的實(shí)驗(yàn)研究. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(3): 282-287. doi: 復(fù)制

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2. Julie A, Lorraine B, Gordon R. The role of the coagulation cascade in the continuum of sepsis and acute lung injury and acute respiratory distress syndrome [J]. Semin Respir Crit Care Med,2006, 27(4):365-376.
3. 周敏, 羅曉明, 杜敏, 等.急性感染性腹膜炎患者外周血內(nèi)毒素水平與急性肺損傷的相關(guān)性分析 [J].肝膽外科雜志, 2010,18(5):358-361..
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5. Hurford WE. The biologic basis for inhaled nitric oxide [J].Respir Care Clin N Am, 1997, 3(3):357-369.
6. 蘇艷軍, 劉其雨, 程若川, 等.新型感染性腹膜炎與急性肺損傷動(dòng)物模型的建立 [J].中華實(shí)驗(yàn)外科雜志, 2007, 24(5):628-630..
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8. 汪建新, 江宏, 薛慶亮, 等.內(nèi)毒索致兔早期急性肺損傷機(jī)制的探討 [J].解放軍醫(yī)學(xué)雜志, 2006, 31(8):758-761..
9. Deitch EA, Berg R. Bacterial translocation from the gut: a mechanism of infection [J]. J Burn Care Rehabil, 1987, 8(6):475-482.
10. 方向, 陳玉祥, 劉震, 等.急性化膿性腹膜炎相關(guān)性腹水對大鼠肝臟的損傷作用研究 [J].中國普外基礎(chǔ)與臨床雜志,2009, 16(7): 555-559..
11. 劉震, 程若川, 方向, 等.PAAF 與ASPAAF 誘導(dǎo)的腸損傷比較的實(shí)驗(yàn)研究 [J].中國普外基礎(chǔ)與臨床雜志, 2008, 15(8):555-559..
12. 徐明舉, 利凱, 崔紅玉, 等.H3N2 豬流感病毒誘導(dǎo)的小鼠急性肺損傷與SOD, NO, MAD 和OH? 變化的相關(guān)性研究 [J].中國病理生理雜志, 2011, 27(4):783-786, 790.
13. Ahmad S, White CW, Chang LY, et a1. Glutamine protects mitochondrial structure and function in oxygen toxicity [J]. Am J Physiol Lung Cell Mol Physiol, 2001, 280(4): L779-L791.
14. 王琳芳, 張磊, 金鑫, 等.一氧化氮對重癥急性胰腺炎肺損傷的作用及其機(jī)制 [J].中華實(shí)驗(yàn)外科雜志, 2007, 24(2):202-204..
15. Boyle WA 3rd, Parvathaneni LS, Bourlier V, et a1. iNOS gene expression modulates microvascular responsiveness in endotoxinchallenged mice [J]. Circ Res, 2000, 87(7): E18-E24.
16. Speyer CL, Neff TA, Warner RL, et al. Regulatory effects of iNOS on acute lung inflammatory responses in mice [J]. Am J Pathol, 2003, 163(6): 2319-2328.
17. 李立萍, 張建新, 李蘭芳, 等.氨基胍對內(nèi)毒素性肺損傷細(xì)胞凋亡的影響 [J].中國藥理學(xué)通報(bào), 2007, 23(1):28-32..
18. Koizumi T, Ogasawara H, Yamamato H, et a1. Effect of ONO1714, a specific inducible nitric oxide synthase inhibitor,on lung lymph filtration and gas exchange during endotoxemia in unanesthetized sheep [J]. Anesthesiology, 2004, 101(1): 59-65.
19. Okamoto I, Abe M, Shibata K, et a1. Evaluating the role of inducible nitric oxide synthase using a novel and selective inducible nitric oxide synthase inhibitor in septic lung injury produced by cecal ligation and puncture [J]. Am J Respir Crit Care Med,2000, 162(2 Pt 1): 716-722.
20. Liu P, Xu B, Hock CE. Inhibition of nitric oxide synthesis by L-name exacerbates acute lung injury induced by hepatic ischemia-reperfusion [J]. Shock, 2001, 16(3): 211-217.
21. 劉壘, 王衛(wèi)星, 余佳, 等.iNOS 及eNOS mRNA 表達(dá)在急性壞死性胰腺炎肺損傷中的作用 [J].中國普外基礎(chǔ)與臨床雜志,2010, 17(5):449-453..
22. Rudkowski JC, Barreiro E, Harfouche R, et a1. Roles of iNOS and nNOS in sepsis-induced pulmonary apoptosis [J]. Am J Physiol Lung Cell Mol Physiol, 2004, 286(4): L793-L800.
23. 李立萍, 張建新, 李蘭芳, 等.LPS 性肺損傷大鼠一氧化氮合酶表達(dá)和肺細(xì)胞凋亡變化 [J].中國病理生理雜志, 2007,23(10):1996-2001..
24. Matute-Bello G, Liles WC,F(xiàn)revert CW, et a1.Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits [J].Am J Physiol Lung Cell Mol Physiol,2001, 281(2):328-335..
25. Nakamura M, Matute-Bello G, Liles WC, et a1. Differential response of human lung epithelial cells to fas-induced apoptosis [J]. Am J Pathol, 2004, 164(6):1949-1958.
  1. 1. Hiki N, Berger D, Mimura Y, et a1. Release of endotoxin-binding proteins during major elective surgery: role of soluble CD14 in phagocytic activation [J]. World J Surg, 2000, 24(5): 499-506.
  2. 2. Julie A, Lorraine B, Gordon R. The role of the coagulation cascade in the continuum of sepsis and acute lung injury and acute respiratory distress syndrome [J]. Semin Respir Crit Care Med,2006, 27(4):365-376.
  3. 3. 周敏, 羅曉明, 杜敏, 等.急性感染性腹膜炎患者外周血內(nèi)毒素水平與急性肺損傷的相關(guān)性分析 [J].肝膽外科雜志, 2010,18(5):358-361..
  4. 4. 吳妍雯. 內(nèi)毒素性急性肺損傷與NO 吸入治療 [J].臨床肺科雜志, 2010, 15(8):1141-1143..
  5. 5. Hurford WE. The biologic basis for inhaled nitric oxide [J].Respir Care Clin N Am, 1997, 3(3):357-369.
  6. 6. 蘇艷軍, 劉其雨, 程若川, 等.新型感染性腹膜炎與急性肺損傷動(dòng)物模型的建立 [J].中華實(shí)驗(yàn)外科雜志, 2007, 24(5):628-630..
  7. 7. 程石, 何三光, 張佳林.肺泡巨噬細(xì)胞活化在急性壞死性胰腺炎大鼠肺損傷中的作用 [J].中華外科雜志, 2002, 40(8):609-612..
  8. 8. 汪建新, 江宏, 薛慶亮, 等.內(nèi)毒索致兔早期急性肺損傷機(jī)制的探討 [J].解放軍醫(yī)學(xué)雜志, 2006, 31(8):758-761..
  9. 9. Deitch EA, Berg R. Bacterial translocation from the gut: a mechanism of infection [J]. J Burn Care Rehabil, 1987, 8(6):475-482.
  10. 10. 方向, 陳玉祥, 劉震, 等.急性化膿性腹膜炎相關(guān)性腹水對大鼠肝臟的損傷作用研究 [J].中國普外基礎(chǔ)與臨床雜志,2009, 16(7): 555-559..
  11. 11. 劉震, 程若川, 方向, 等.PAAF 與ASPAAF 誘導(dǎo)的腸損傷比較的實(shí)驗(yàn)研究 [J].中國普外基礎(chǔ)與臨床雜志, 2008, 15(8):555-559..
  12. 12. 徐明舉, 利凱, 崔紅玉, 等.H3N2 豬流感病毒誘導(dǎo)的小鼠急性肺損傷與SOD, NO, MAD 和OH? 變化的相關(guān)性研究 [J].中國病理生理雜志, 2011, 27(4):783-786, 790.
  13. 13. Ahmad S, White CW, Chang LY, et a1. Glutamine protects mitochondrial structure and function in oxygen toxicity [J]. Am J Physiol Lung Cell Mol Physiol, 2001, 280(4): L779-L791.
  14. 14. 王琳芳, 張磊, 金鑫, 等.一氧化氮對重癥急性胰腺炎肺損傷的作用及其機(jī)制 [J].中華實(shí)驗(yàn)外科雜志, 2007, 24(2):202-204..
  15. 15. Boyle WA 3rd, Parvathaneni LS, Bourlier V, et a1. iNOS gene expression modulates microvascular responsiveness in endotoxinchallenged mice [J]. Circ Res, 2000, 87(7): E18-E24.
  16. 16. Speyer CL, Neff TA, Warner RL, et al. Regulatory effects of iNOS on acute lung inflammatory responses in mice [J]. Am J Pathol, 2003, 163(6): 2319-2328.
  17. 17. 李立萍, 張建新, 李蘭芳, 等.氨基胍對內(nèi)毒素性肺損傷細(xì)胞凋亡的影響 [J].中國藥理學(xué)通報(bào), 2007, 23(1):28-32..
  18. 18. Koizumi T, Ogasawara H, Yamamato H, et a1. Effect of ONO1714, a specific inducible nitric oxide synthase inhibitor,on lung lymph filtration and gas exchange during endotoxemia in unanesthetized sheep [J]. Anesthesiology, 2004, 101(1): 59-65.
  19. 19. Okamoto I, Abe M, Shibata K, et a1. Evaluating the role of inducible nitric oxide synthase using a novel and selective inducible nitric oxide synthase inhibitor in septic lung injury produced by cecal ligation and puncture [J]. Am J Respir Crit Care Med,2000, 162(2 Pt 1): 716-722.
  20. 20. Liu P, Xu B, Hock CE. Inhibition of nitric oxide synthesis by L-name exacerbates acute lung injury induced by hepatic ischemia-reperfusion [J]. Shock, 2001, 16(3): 211-217.
  21. 21. 劉壘, 王衛(wèi)星, 余佳, 等.iNOS 及eNOS mRNA 表達(dá)在急性壞死性胰腺炎肺損傷中的作用 [J].中國普外基礎(chǔ)與臨床雜志,2010, 17(5):449-453..
  22. 22. Rudkowski JC, Barreiro E, Harfouche R, et a1. Roles of iNOS and nNOS in sepsis-induced pulmonary apoptosis [J]. Am J Physiol Lung Cell Mol Physiol, 2004, 286(4): L793-L800.
  23. 23. 李立萍, 張建新, 李蘭芳, 等.LPS 性肺損傷大鼠一氧化氮合酶表達(dá)和肺細(xì)胞凋亡變化 [J].中國病理生理雜志, 2007,23(10):1996-2001..
  24. 24. Matute-Bello G, Liles WC,F(xiàn)revert CW, et a1.Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits [J].Am J Physiol Lung Cell Mol Physiol,2001, 281(2):328-335..
  25. 25. Nakamura M, Matute-Bello G, Liles WC, et a1. Differential response of human lung epithelial cells to fas-induced apoptosis [J]. Am J Pathol, 2004, 164(6):1949-1958.