• 成都軍區(qū)總醫(yī)院全軍普通外科中心,四川成都 610083;

目的:研究離體肝臟缺血再灌注期間絲裂原活化蛋白激酶(mitogen activated protein kinase,p38MAPK)信號(hào)轉(zhuǎn)導(dǎo)途徑對(duì)細(xì)胞間黏附分子1(intercellular adhesion molecular 1,ICAM1)mRNA表達(dá)的影響。方法:建立兔離體肝臟缺血再灌注模型,對(duì)照組(n=12):灌注液中不加特異性p38MAPK抑制劑SB202190,抑制組(n=12):灌注液中加入SB202190(濃度為3μmol/L)。于肝臟離體前,冷保存末,再灌注10min、30min、60min及120min時(shí)獲取離體肝組織標(biāo)本。分別應(yīng)用Western-blot法及免疫沉淀法檢測(cè)離體肝組織中p38MAPK表達(dá)的水平及活性,原位雜交法檢測(cè)ICAM1 mRNA表達(dá)水平。結(jié)果:與離體前相較,對(duì)照組p38MAPK活性在冷保存末及再灌注10min、30min、60min顯著性增高(P lt;0.01),而再灌注120min時(shí)活性與離體前相較無明顯差異(P gt;0.05);抑制組p38MAPK活性在各時(shí)相點(diǎn)的變化無顯著性差異(P gt;0.05),除離體前及再灌注120min兩組肝臟的p38MAPK活性無顯著性差異外,其余各時(shí)相點(diǎn)p38MAPK活性均顯著性低于對(duì)照組(P lt;0.01)。離體前、冷保存末及再灌注10min及30min時(shí),兩組肝組織中僅有少量ICAM1 mRNA表達(dá),組間及組內(nèi)比較無顯著性差異(P gt;0.05);至再灌注60min及120min,對(duì)照組ICAM1 mRNA的表達(dá)水平顯著性高于組內(nèi)其它時(shí)相點(diǎn)(P lt;0.01),而抑制組雖然也顯著高于組內(nèi)其它時(shí)相點(diǎn)(P lt;0.05),但卻顯著性低于同時(shí)相點(diǎn)對(duì)照組的表達(dá)水平(P lt;0.01)。離體再灌注期間供肝組織中p38MAPK活性與供肝組織內(nèi)ICAM1 mRNA的表達(dá)水平呈顯著性正相關(guān)(r=0.985,P lt;0.01)。結(jié)論:p38MAPK對(duì)ICAM1生成的調(diào)節(jié)作用層次可能在轉(zhuǎn)錄水平,提示p38MAPK信號(hào)轉(zhuǎn)導(dǎo)途徑對(duì)ICAM1 mRNA的調(diào)節(jié)可能是導(dǎo)致離體肝臟缺血再灌注損傷的重要機(jī)制之一。

引用本文： 王雨,湯禮軍,戴睿武,閻勇. p38MAPK信號(hào)轉(zhuǎn)導(dǎo)途徑對(duì)早期缺血再灌注期間離體肝臟ICAM1 mRNA表達(dá)的影響. 華西醫(yī)學(xué), 2009, 24(8): 2087-2091. doi: 復(fù)制

1. 王雨,田伏洲,湯禮軍,等.P38信號(hào)轉(zhuǎn)導(dǎo)途徑對(duì)離體肝臟缺血再灌注損傷的影響[J].中華肝臟病雜志,2003,11(3):170-172.
2. JAESCHKE H, FARHOOD A. Neutrophil and Kupffer cellinduced oxidant stress and ischemia reperfusion injury in rat liver[J]. Am J Physiol,1991,260(3 Pt 1):G355.
3. 冉江華,郭永章,李立,等.重組人生長(zhǎng)激素對(duì)大鼠肝臟缺血再灌注損傷的保護(hù)作用[J].中國普外基礎(chǔ)與臨床雜志,2006,13(5):555.
4. JAMIESON N V, LINDELL S, SUNDBERG R, et al. An analysis of the components in UW solution using the isolated perfused rabbit liver[J]. Transplantation,1988,46(3):512.
5. 湯禮軍,田伏洲,王雨,等.缺血再灌注肝臟組織中ICAM1基因的表達(dá)[J].中國病理生理雜志,2001,17(12):1246.
6. LEE J C, LAYDON J T, MCDONNELL P C, et al. Identification and characterization of a novel protein kinase involved in the regulation of inflammatory cytokine biosynthesis[J]. Nature,1994,372:739-746.
7. LEE J C, KASSIS S, KUMAR S, et al. p38 mitogenactivated protein kinase inhibitorsmechanisms and therapeutic potentials[J]. Pharmacol Ther,1999,82(2-3):389-397.
8. LISNOCK J, TEBBEN A, FRANTZ B, et al. Molecular basis for p38 protein kinase inhibitor specificity[J]. Biochemistry,1998,37(47):16573-16581.
9. 姜勇.MAPK信號(hào)轉(zhuǎn)導(dǎo)通路對(duì)炎癥反應(yīng)的調(diào)控[J].生理學(xué)報(bào),2000,52(4):267-271.
10. CHEN X L, XIA Z F, BEN D F, et al. Role of p38 mitogenactivated protein kinase in lung injury after burn trauma[J]. Shock,2003,19(5):475.
11. BHARGAVA A, BRADLEY N J, BURROUGHS A K, et al. Expression of intercellular adhesion molecule1 and CD4/CD8 lymphocyte markers in perioperative liver allograft biopsies[J]. Transplant Proc,1995,27(5):2814.
12. SAMAN A, IRIS G, GREGORY J B, et al. Alcohol (Ethanol) inhibits IL8 and TNF: Role of the p38 pathway[J]. J Immunol,1999,162(6):7441.
13. HAFEA T, MOUSSAM, NESIM I, et al. The effect of intraportal prostaglandinE1 on adhesion molecule expression, inflammatory modulator function and histology in canine hepatic ischemia/reperfusion injury[J]. J Surg Res,2007,138(1):88.
14. 徐鋒,蘇琪,戴朝六,等.前列腺素E1對(duì)梗阻性黃疸肝缺血再灌注時(shí)肝組織細(xì)胞間黏附分子1表達(dá)的影響[J].廣東醫(yī)學(xué),2009,30(1):37.
15. 袁曉園,陳隆典.肝免疫耐受發(fā)生的相關(guān)因素和機(jī)制研究[J].國際免疫學(xué)雜志,2006,29(1):26.
16. 張維山,冷啟新,王金平,等.轉(zhuǎn)錄因子NFκB在內(nèi)毒素休克中的作用[J].解剖科學(xué)進(jìn)展,2005,11(2):161.
17. 劉佃香.慢性乙型肝炎及乙肝肝硬化患者的血小板功能相關(guān)性分析[J].醫(yī)學(xué)理論與實(shí)踐,2008,21(8):959.
18. 劉少華,馬可,許兵,等.一氧化碳對(duì)脂多糖誘導(dǎo)大鼠腸道損傷的影響[J].中國普外基礎(chǔ)與臨床雜志,2008,15(3):174.
19. YAN W, ZHAO K, JIANG Y, et al. Role of p38MAPK in ICAM1 expression of vascular endothelial cells induced by lipopolysaccharide[J]. Shock,2002,17(5):433.
20. DOUGLAS Y T, ERNEST E M, JEFFREY L J, et al. p38 mitogenactivated protein kinase inhibition attenuates intercellular adhesion molecule1 upregulation on human pulmonary microvascular endothelial cells[J]. Surgery,1998,124(2):403.
21. RACHID K, JOEL S K, FARID K, et al. Expression and regulation of adhesion molecules in cardiac cells by cytokines response to acute hypoxia[J]. Circ Res,1998,82(3):576.
22. 崔堯元,余勇,張曉彪,等.細(xì)胞間黏附分子1腫瘤壞死因子α轉(zhuǎn)錄水平在缺血再灌注大鼠腦皮質(zhì)中表達(dá)的相關(guān)性[J].中華實(shí)驗(yàn)外科雜志,1999,16(5):442.
23. SAHA R N, JANA M, PAHAN K. MAPK p38 regulates transcriptional activity of NFκB in primary human astrocytes via acetylation of p65[J]. J Immunol,2007,179(10):7101.
24. SON C M, HEDRICK M N, IZADI H, et al. p38 mitogenactivated protein kinase controls NFκB transcriptional activation and tumor necrosis factor α production through RelA phosphorylation mediated by mitogen and stressactivated protein kinase 1 in response to Borrelia burgdorferi antigens[J]. Infect Immun,2007,75(1):270.
25. 陳旭林,夏照帆,賈一韜,等.p38絲裂原活化蛋白激酶對(duì)嚴(yán)重?zé)齻笫蟾闻K激活蛋白-1和核因子-κB的影響[J].中華損傷與修復(fù)雜志(電子版),2008,3(2):150.
26. 馬躍峰,李相成,姚愛華,等.缺血預(yù)處理對(duì)大鼠肝臟移植物再灌注早期NF-κB活性的影響及意義[J].中國普外基礎(chǔ)與臨床雜志,2006,13(5):531.
  1. 1. 王雨,田伏洲,湯禮軍,等.P38信號(hào)轉(zhuǎn)導(dǎo)途徑對(duì)離體肝臟缺血再灌注損傷的影響[J].中華肝臟病雜志,2003,11(3):170-172.
  2. 2. JAESCHKE H, FARHOOD A. Neutrophil and Kupffer cellinduced oxidant stress and ischemia reperfusion injury in rat liver[J]. Am J Physiol,1991,260(3 Pt 1):G355.
  3. 3. 冉江華,郭永章,李立,等.重組人生長(zhǎng)激素對(duì)大鼠肝臟缺血再灌注損傷的保護(hù)作用[J].中國普外基礎(chǔ)與臨床雜志,2006,13(5):555.
  4. 4. JAMIESON N V, LINDELL S, SUNDBERG R, et al. An analysis of the components in UW solution using the isolated perfused rabbit liver[J]. Transplantation,1988,46(3):512.
  5. 5. 湯禮軍,田伏洲,王雨,等.缺血再灌注肝臟組織中ICAM1基因的表達(dá)[J].中國病理生理雜志,2001,17(12):1246.
  6. 6. LEE J C, LAYDON J T, MCDONNELL P C, et al. Identification and characterization of a novel protein kinase involved in the regulation of inflammatory cytokine biosynthesis[J]. Nature,1994,372:739-746.
  7. 7. LEE J C, KASSIS S, KUMAR S, et al. p38 mitogenactivated protein kinase inhibitorsmechanisms and therapeutic potentials[J]. Pharmacol Ther,1999,82(2-3):389-397.
  8. 8. LISNOCK J, TEBBEN A, FRANTZ B, et al. Molecular basis for p38 protein kinase inhibitor specificity[J]. Biochemistry,1998,37(47):16573-16581.
  9. 9. 姜勇.MAPK信號(hào)轉(zhuǎn)導(dǎo)通路對(duì)炎癥反應(yīng)的調(diào)控[J].生理學(xué)報(bào),2000,52(4):267-271.
  10. 10. CHEN X L, XIA Z F, BEN D F, et al. Role of p38 mitogenactivated protein kinase in lung injury after burn trauma[J]. Shock,2003,19(5):475.
  11. 11. BHARGAVA A, BRADLEY N J, BURROUGHS A K, et al. Expression of intercellular adhesion molecule1 and CD4/CD8 lymphocyte markers in perioperative liver allograft biopsies[J]. Transplant Proc,1995,27(5):2814.
  12. 12. SAMAN A, IRIS G, GREGORY J B, et al. Alcohol (Ethanol) inhibits IL8 and TNF: Role of the p38 pathway[J]. J Immunol,1999,162(6):7441.
  13. 13. HAFEA T, MOUSSAM, NESIM I, et al. The effect of intraportal prostaglandinE1 on adhesion molecule expression, inflammatory modulator function and histology in canine hepatic ischemia/reperfusion injury[J]. J Surg Res,2007,138(1):88.
  14. 14. 徐鋒,蘇琪,戴朝六,等.前列腺素E1對(duì)梗阻性黃疸肝缺血再灌注時(shí)肝組織細(xì)胞間黏附分子1表達(dá)的影響[J].廣東醫(yī)學(xué),2009,30(1):37.
  15. 15. 袁曉園,陳隆典.肝免疫耐受發(fā)生的相關(guān)因素和機(jī)制研究[J].國際免疫學(xué)雜志,2006,29(1):26.
  16. 16. 張維山,冷啟新,王金平,等.轉(zhuǎn)錄因子NFκB在內(nèi)毒素休克中的作用[J].解剖科學(xué)進(jìn)展,2005,11(2):161.
  17. 17. 劉佃香.慢性乙型肝炎及乙肝肝硬化患者的血小板功能相關(guān)性分析[J].醫(yī)學(xué)理論與實(shí)踐,2008,21(8):959.
  18. 18. 劉少華,馬可,許兵,等.一氧化碳對(duì)脂多糖誘導(dǎo)大鼠腸道損傷的影響[J].中國普外基礎(chǔ)與臨床雜志,2008,15(3):174.
  19. 19. YAN W, ZHAO K, JIANG Y, et al. Role of p38MAPK in ICAM1 expression of vascular endothelial cells induced by lipopolysaccharide[J]. Shock,2002,17(5):433.
  20. 20. DOUGLAS Y T, ERNEST E M, JEFFREY L J, et al. p38 mitogenactivated protein kinase inhibition attenuates intercellular adhesion molecule1 upregulation on human pulmonary microvascular endothelial cells[J]. Surgery,1998,124(2):403.
  21. 21. RACHID K, JOEL S K, FARID K, et al. Expression and regulation of adhesion molecules in cardiac cells by cytokines response to acute hypoxia[J]. Circ Res,1998,82(3):576.
  22. 22. 崔堯元,余勇,張曉彪,等.細(xì)胞間黏附分子1腫瘤壞死因子α轉(zhuǎn)錄水平在缺血再灌注大鼠腦皮質(zhì)中表達(dá)的相關(guān)性[J].中華實(shí)驗(yàn)外科雜志,1999,16(5):442.
  23. 23. SAHA R N, JANA M, PAHAN K. MAPK p38 regulates transcriptional activity of NFκB in primary human astrocytes via acetylation of p65[J]. J Immunol,2007,179(10):7101.
  24. 24. SON C M, HEDRICK M N, IZADI H, et al. p38 mitogenactivated protein kinase controls NFκB transcriptional activation and tumor necrosis factor α production through RelA phosphorylation mediated by mitogen and stressactivated protein kinase 1 in response to Borrelia burgdorferi antigens[J]. Infect Immun,2007,75(1):270.
  25. 25. 陳旭林,夏照帆,賈一韜,等.p38絲裂原活化蛋白激酶對(duì)嚴(yán)重?zé)齻笫蟾闻K激活蛋白-1和核因子-κB的影響[J].中華損傷與修復(fù)雜志(電子版),2008,3(2):150.
  26. 26. 馬躍峰,李相成,姚愛華,等.缺血預(yù)處理對(duì)大鼠肝臟移植物再灌注早期NF-κB活性的影響及意義[J].中國普外基礎(chǔ)與臨床雜志,2006,13(5):531.