• 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)信號轉導途徑對腫瘤壞死因子α (tumor necrosis factor α,TNFα )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)。分別于肝臟離體前,冷保存末,再灌注10min、30min、60min及120min時獲取離體肝組織標本。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,RT-PCR法檢測TNF-α-mRNA表達水平。結果:對照組p38MAPK活性在冷保存末及再灌注10min、30min、60min均較離體前和再灌注120min顯著升高(P lt;0.01),也顯著高于同時相點的抑制組(P lt;0.01);抑制組p38MAPK活性在組內(nèi)各時相點的變化無顯著性差異(P gt;0.05)。兩組肝臟于離體前、冷保存末及再灌注10min及30min,肝組織中僅有少量TNF-α mRNA表達,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,對照組TNF-α mRNA的表達水平顯著性高于組內(nèi)其它時相點(P lt;0.01),而抑制組雖然也顯著高于組內(nèi)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(nèi)TNF-α mRNA的表達水平呈顯著性正相關(r=0.996,P lt;0.01)。結論:p38MAPK對TNF-α生成的調節(jié)作用層次可能在轉錄水平,提示p38MAPK信號轉導途徑對TNF-α mRNA的調節(jié)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. 離體肝臟早期缺血再灌注期間p38信號轉導途徑對TNFα mRNA表達的影響. 華西醫(yī)學, 2009, 24(6): 1475-1479. doi: 復制

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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.
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. 黃翠萍,楊和平,張珍祥,等.p38蛋白激酶對支氣管哮喘大鼠Th2類細胞因子表達的調控[J].中國病理生理雜志,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,劉愛華,張琳,等.脂多糖激活p38在誘導腫瘤壞死因子α基因表達中的作用[J].中華醫(yī)學雜志,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,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..
24. 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..
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  9. 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. 10. 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..
  11. 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. 12. 簡文,樊愛琳,尹文,等.山莨菪堿治療兔創(chuàng)傷性急性肺損傷分子生物學機制的實驗研究[J].第四軍醫(yī)大學學報,2008,29(11):985..
  13. 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. 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. 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. 16. 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.
  17. 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. 18. 黃翠萍,楊和平,張珍祥,等.p38蛋白激酶對支氣管哮喘大鼠Th2類細胞因子表達的調控[J].中國病理生理雜志,2006,22(2):311..
  19. 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. 20. 姜勇,劉愛華,張琳,等.脂多糖激活p38在誘導腫瘤壞死因子α基因表達中的作用[J].中華醫(yī)學雜志,1999,79(5):360..
  21. 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. 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. 23. 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..
  24. 24. 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..