p38MAPK信號轉導途徑對早期缺血再灌注期間離體肝臟ICAM1 mRNA表達的影響_《華西醫學》

作者：

 王雨 , 湯禮軍 , 戴睿武 , 閻勇

成都軍區總醫院全軍普通外科中心,四川成都 610083;

關鍵詞：

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。

引用本文： 王雨,湯禮軍,戴睿武,閻勇. p38MAPK信號轉導途徑對早期缺血再灌注期間離體肝臟ICAM1 mRNA表達的影響. 華西醫學, 2009, 24(8): 2087-2091. doi: 復制

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.

《華西醫學》

p38MAPK信號轉導途徑對早期缺血再灌注期間離體肝臟ICAM1 mRNA表達的影響

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《華西醫學》

p38MAPK信號轉導途徑對早期缺血再灌注期間離體肝臟ICAM1 mRNA表達的影響

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料