Effect of p38MAPK Pathway on ICAM1 mRNA Expression of Isolated Rabbit Liver Tissue during Early Stage of Cold Preservation and Reperfusion Period_West China Medical Journal

Authors：

 WANG Yu , TANG Lijun , DAI Ruiwu , et al

the General Surgery Center of PLA, General Hospital of Chengdu Military Region, Chengdu 610083, China;

Corresponding?author：

WANG Yu, Email: wangyu_rick@163.com

Keywords：

肝; 缺血再灌注; 損傷; 絲裂原活化蛋白激酶; 細胞間黏附分子; 抑制劑

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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)信號轉導途徑對細胞間黏附分子1(intercellular adhesion molecular 1,ICAM1)mRNA表達的影響。方法:建立兔離體肝臟缺血再灌注模型,對照組(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時獲取離體肝組織標本。分別應用Western-blot法及免疫沉淀法檢測離體肝組織中p38MAPK表達的水平及活性,原位雜交法檢測ICAM1 mRNA表達水平。結果:與離體前相較,對照組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活性在各時相點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,其余各時相點p38MAPK活性均顯著性低于對照組(P lt;0.01)。離體前、冷保存末及再灌注10min及30min時,兩組肝組織中僅有少量ICAM1 mRNA表達,組間及組內比較無顯著性差異(P gt;0.05);至再灌注60min及120min,對照組ICAM1 mRNA的表達水平顯著性高于組內其它時相點(P lt;0.01),而抑制組雖然也顯著高于組內其它時相點(P lt;0.05),但卻顯著性低于同時相點對照組的表達水平(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ICAM1 mRNA的表達水平呈顯著性正相關(r=0.985,P lt;0.01)。結論:p38MAPK對ICAM1生成的調節作用層次可能在轉錄水平,提示p38MAPK信號轉導途徑對ICAM1 mRNA的調節可能是導致離體肝臟缺血再灌注損傷的重要機制之一。

Citation： WANG Yu,TANG Lijun,DAI Ruiwu,et al. Effect of p38MAPK Pathway on ICAM1 mRNA Expression of Isolated Rabbit Liver Tissue during Early Stage of Cold Preservation and Reperfusion Period. West China Medical Journal, 2009, 24(8): 2087-2091. doi: Copy

1.	王雨,田伏洲,湯禮軍,等.P38信號轉導途徑對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.重組人生長激素對大鼠肝臟缺血再灌注損傷的保護作用[J].中國普外基礎與臨床雜志,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[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信號轉導通路對炎癥反應的調控[J].生理學報,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對梗阻性黃疸肝缺血再灌注時肝組織細胞間黏附分子1表達的影響[J].廣東醫學,2009,30(1):37.
15.	袁曉園,陳隆典.肝免疫耐受發生的相關因素和機制研究[J].國際免疫學雜志,2006,29(1):26.
16.	張維山,冷啟新,王金平,等.轉錄因子NFκB在內毒素休克中的作用[J].解剖科學進展,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性分析[J].醫學理論與實踐,2008,21(8):959.
18.	劉少華,馬可,許兵,等.一氧化碳對脂多糖誘導大鼠腸道損傷的影響[J].中國普外基礎與臨床雜志,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.細胞間黏附分子1腫瘤壞死因子α轉錄水平在缺血再灌注大鼠腦皮質中表達的相關性[J].中華實驗外科雜志,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嚴重燒傷大鼠肝臟激活蛋白-1和核因子-κB的影響[J].中華損傷與修復雜志(電子版),2008,3(2):150.
26.	馬躍峰,李相成,姚愛華,等.缺血預處理對大鼠肝臟移植物再灌注早期NF-κB活性的影響及意義[J].中國普外基礎與臨床雜志,2006,13(5):531.

1. 王雨,田伏洲,湯禮軍,等.P38信號轉導途徑對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.重組人生長激素對大鼠肝臟缺血再灌注損傷的保護作用[J].中國普外基礎與臨床雜志,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[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信號轉導通路對炎癥反應的調控[J].生理學報,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對梗阻性黃疸肝缺血再灌注時肝組織細胞間黏附分子1表達的影響[J].廣東醫學,2009,30(1):37.
15. 袁曉園,陳隆典.肝免疫耐受發生的相關因素和機制研究[J].國際免疫學雜志,2006,29(1):26.
16. 張維山,冷啟新,王金平,等.轉錄因子NFκB在內毒素休克中的作用[J].解剖科學進展,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性分析[J].醫學理論與實踐,2008,21(8):959.
18. 劉少華,馬可,許兵,等.一氧化碳對脂多糖誘導大鼠腸道損傷的影響[J].中國普外基礎與臨床雜志,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.細胞間黏附分子1腫瘤壞死因子α轉錄水平在缺血再灌注大鼠腦皮質中表達的相關性[J].中華實驗外科雜志,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嚴重燒傷大鼠肝臟激活蛋白-1和核因子-κB的影響[J].中華損傷與修復雜志(電子版),2008,3(2):150.
26. 馬躍峰,李相成,姚愛華,等.缺血預處理對大鼠肝臟移植物再灌注早期NF-κB活性的影響及意義[J].中國普外基礎與臨床雜志,2006,13(5):531.

West China Medical Journal

Effect of p38MAPK Pathway on ICAM1 mRNA Expression of Isolated Rabbit Liver Tissue during Early Stage of Cold Preservation and Reperfusion Period

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