Effect of p38 MAPK Pathway on TNFα 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; 肿瘤坏死因子; 抑制剂

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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)信号转导途径对肿瘤坏死因子α (tumor necrosis factor α,TNFα )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)。分别于肝脏离体前,冷保存末,再灌注10min、30min、60min及120min时获取离体肝组织标本。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,RT-PCR法检测TNF-α-mRNA表达水平。结果:对照组p38MAPK活性在冷保存末及再灌注10min、30min、60min均较离体前和再灌注120min显著升高(P lt;0.01),也显著高于同时相点的抑制组(P lt;0.01);抑制组p38MAPK活性在组内各时相点的变化无显著性差异(P gt;0.05)。两组肝脏于离体前、冷保存末及再灌注10min及30min,肝组织中仅有少量TNF-α 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TNF-α 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TNF-α mRNA的表达水平呈显著性正相关(r=0.996,P lt;0.01)。结论:p38MAPK对TNF-α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TNF-α 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 p38 MAPK Pathway on TNFα mRNA Expression of Isolated Rabbit Liver Tissue during Early Stage of Cold Preservation and Reperfusion Period. West China Medical Journal, 2009, 24(6): 1475-1479. doi: Copy

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8.	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..
9.	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..
10.	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..
11.	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..
12.	简文,樊爱琳,尹文,等.山莨菪碱治疗兔创伤性急性肺损伤分子生物学机制的实验研究[J].第四军医大学学报,2008,29(11):985..
13.	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..
14.	DAWS, HALLENBECK J M. Inhibition of tumor necrosis factorα reduces focal cerebral ischemic injury in the spontaneously hypertensive rat[J]. Neurosci Lett,1996,218(1):41.
15.	DINARELLO C A, IKEJIMA T, WARNER S J, et al. Interleukin 1 induces interleukin 1 induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro[J]. J Immunol,1987,139(6):1902..
16.	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.
17.	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..
18.	黄翠萍,杨和平,张珍祥,等.p38蛋白激酶对支气管哮喘大鼠Th2类细胞因子表达的调控[J].中国病理生理杂志,2006,22(2):311..
19.	TUDHOPE S J, FINNEYHAYWARD T K, NICHOLSON A G, et al. Different mitogenactivated protein kinasedependent cytokine responses in cells of the monocyte lineage[J]. J Pharmacol Exp Ther,2008,324(1):306..
20.	姜勇,刘爱华,张琳,等.脂多糖激活p38在诱导肿瘤坏死因子α基因表达中的作用[J].中华医学杂志,1999,79(5):360..
21.	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..
22.	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..
23.	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..
24.	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.
2.
3.
4.
5.
6.
7.
8. 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..
9. 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..
10. 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..
11. 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..
12. 简文,樊爱琳,尹文,等.山莨菪碱治疗兔创伤性急性肺损伤分子生物学机制的实验研究[J].第四军医大学学报,2008,29(11):985..
13. 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..
14. DAWS, HALLENBECK J M. Inhibition of tumor necrosis factorα reduces focal cerebral ischemic injury in the spontaneously hypertensive rat[J]. Neurosci Lett,1996,218(1):41.
15. DINARELLO C A, IKEJIMA T, WARNER S J, et al. Interleukin 1 induces interleukin 1 induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro[J]. J Immunol,1987,139(6):1902..
16. 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.
17. 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..
18. 黄翠萍,杨和平,张珍祥,等.p38蛋白激酶对支气管哮喘大鼠Th2类细胞因子表达的调控[J].中国病理生理杂志,2006,22(2):311..
19. TUDHOPE S J, FINNEYHAYWARD T K, NICHOLSON A G, et al. Different mitogenactivated protein kinasedependent cytokine responses in cells of the monocyte lineage[J]. J Pharmacol Exp Ther,2008,324(1):306..
20. 姜勇,刘爱华,张琳,等.脂多糖激活p38在诱导肿瘤坏死因子α基因表达中的作用[J].中华医学杂志,1999,79(5):360..
21. 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..
22. 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..
23. 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..
24. 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 p38 MAPK Pathway on TNFα mRNA Expression of Isolated Rabbit Liver Tissue during Early Stage of Cold Preservation and Reperfusion Period

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