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; 损伤; 丝裂原活化蛋白激酶; 细胞间黏附分子; 抑制剂

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

目的:研究离体肝脏缺血再灌注期间丝裂原活化蛋白激酶(mitogen activated protein kinase,p38MAPK)信号转导途径对细胞间黏附分子1(intercellular adhesion molecular 1,ICAM1)mRNA表达的影响。方法:建立兔离体肝脏缺血再灌注模型,对照组(n=12):灌注液中不加特异性p38MAPK抑制剂SB202190,抑制组(n=12):灌注液中加入SB202190(浓度为3μmol/L)。于肝脏离体前,冷保存末,再灌注10min、30min、60min及120min时获取离体肝组织标本。分别应用Western-blot法及免疫沉淀法检测离体肝组织中p38MAPK表达的水平及活性,原位杂交法检测ICAM1 mRNA表达水平。结果:与离体前相较,对照组p38MAPK活性在冷保存末及再灌注10min、30min、60min显著性增高(P lt;0.01),而再灌注120min时活性与离体前相较无明显差异(P gt;0.05);抑制组p38MAPK活性在各时相点的变化无显著性差异(P gt;0.05),除离体前及再灌注120min两组肝脏的p38MAPK活性无显著性差异外,其余各时相点p38MAPK活性均显著性低于对照组(P lt;0.01)。离体前、冷保存末及再灌注10min及30min时,两组肝组织中仅有少量ICAM1 mRNA表达,组间及组内比较无显著性差异(P gt;0.05);至再灌注60min及120min,对照组ICAM1 mRNA的表达水平显著性高于组内其它时相点(P lt;0.01),而抑制组虽然也显著高于组内其它时相点(P lt;0.05),但却显著性低于同时相点对照组的表达水平(P lt;0.01)。离体再灌注期间供肝组织中p38MAPK活性与供肝组织内ICAM1 mRNA的表达水平呈显著性正相关(r=0.985,P lt;0.01)。结论:p38MAPK对ICAM1生成的调节作用层次可能在转录水平,提示p38MAPK信号转导途径对ICAM1 mRNA的调节可能是导致离体肝脏缺血再灌注损伤的重要机制之一。

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,汤礼军,等.P38信号转导途径对离体肝脏缺血再灌注损伤的影响[J].中华肝脏病杂志,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.	冉江华,郭永章,李立,等.重组人生长激素对大鼠肝脏缺血再灌注损伤的保护作用[J].中国普外基础与临床杂志,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.	汤礼军,田伏洲,王雨,等.缺血再灌注肝脏组织中ICAM1基因的表达[J].中国病理生理杂志,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信号转导通路对炎症反应的调控[J].生理学报,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.	徐锋,苏琪,戴朝六,等.前列腺素E1对梗阻性黄疸肝缺血再灌注时肝组织细胞间黏附分子1表达的影响[J].广东医学,2009,30(1):37.
15.	袁晓园,陈隆典.肝免疫耐受发生的相关因素和机制研究[J].国际免疫学杂志,2006,29(1):26.
16.	张维山,冷启新,王金平,等.转录因子NFκB在内毒素休克中的作用[J].解剖科学进展,2005,11(2):161.
17.	刘佃香.慢性乙型肝炎及乙肝肝硬化患者的血小板功能相关性分析[J].医学理论与实践,2008,21(8):959.
18.	刘少华,马可,许兵,等.一氧化碳对脂多糖诱导大鼠肠道损伤的影响[J].中国普外基础与临床杂志,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.	崔尧元,余勇,张晓彪,等.细胞间黏附分子1肿瘤坏死因子α转录水平在缺血再灌注大鼠脑皮质中表达的相关性[J].中华实验外科杂志,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.	陈旭林,夏照帆,贾一韬,等.p38丝裂原活化蛋白激酶对严重烧伤大鼠肝脏激活蛋白-1和核因子-κB的影响[J].中华损伤与修复杂志(电子版),2008,3(2):150.
26.	马跃峰,李相成,姚爱华,等.缺血预处理对大鼠肝脏移植物再灌注早期NF-κB活性的影响及意义[J].中国普外基础与临床杂志,2006,13(5):531.

1. 王雨,田伏洲,汤礼军,等.P38信号转导途径对离体肝脏缺血再灌注损伤的影响[J].中华肝脏病杂志,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. 冉江华,郭永章,李立,等.重组人生长激素对大鼠肝脏缺血再灌注损伤的保护作用[J].中国普外基础与临床杂志,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. 汤礼军,田伏洲,王雨,等.缺血再灌注肝脏组织中ICAM1基因的表达[J].中国病理生理杂志,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信号转导通路对炎症反应的调控[J].生理学报,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. 徐锋,苏琪,戴朝六,等.前列腺素E1对梗阻性黄疸肝缺血再灌注时肝组织细胞间黏附分子1表达的影响[J].广东医学,2009,30(1):37.
15. 袁晓园,陈隆典.肝免疫耐受发生的相关因素和机制研究[J].国际免疫学杂志,2006,29(1):26.
16. 张维山,冷启新,王金平,等.转录因子NFκB在内毒素休克中的作用[J].解剖科学进展,2005,11(2):161.
17. 刘佃香.慢性乙型肝炎及乙肝肝硬化患者的血小板功能相关性分析[J].医学理论与实践,2008,21(8):959.
18. 刘少华,马可,许兵,等.一氧化碳对脂多糖诱导大鼠肠道损伤的影响[J].中国普外基础与临床杂志,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. 崔尧元,余勇,张晓彪,等.细胞间黏附分子1肿瘤坏死因子α转录水平在缺血再灌注大鼠脑皮质中表达的相关性[J].中华实验外科杂志,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. 陈旭林,夏照帆,贾一韬,等.p38丝裂原活化蛋白激酶对严重烧伤大鼠肝脏激活蛋白-1和核因子-κB的影响[J].中华损伤与修复杂志(电子版),2008,3(2):150.
26. 马跃峰,李相成,姚爱华,等.缺血预处理对大鼠肝脏移植物再灌注早期NF-κB活性的影响及意义[J].中国普外基础与临床杂志,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

Abstract Full text Figures/Tables Video References Cited by

Format

Content