• 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(hào)轉(zhuǎn)導(dǎo)途徑對(duì)腫瘤壞死因子α (tumor necrosis factor α,TNFα )mRNA表達(dá)的影響。方法:建立兔離體肝臟缺血再灌注模型,對(duì)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(shí)獲取離體肝組織標(biāo)本。應(yīng)用Western-blot法及免疫沉淀法檢測(cè)離體肝組織中p38MAPK表達(dá)的水平及活性,RT-PCR法檢測(cè)TNF-α-mRNA表達(dá)水平。結(jié)果:對(duì)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(shí)相點(diǎn)的抑制組(P lt;0.01);抑制組p38MAPK活性在組內(nèi)各時(shí)相點(diǎn)的變化無(wú)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(dá),組間及組內(nèi)比較無(wú)顯著性差異(P gt;0.05);至再灌注60min及120min,對(duì)照組TNF-α mRNA的表達(dá)水平顯著性高于組內(nèi)其它時(shí)相點(diǎn)(P lt;0.01),而抑制組雖然也顯著高于組內(nèi)其它時(shí)相點(diǎn)(P lt;0.05),但卻顯著性低于同時(shí)相點(diǎn)對(duì)照組的表達(dá)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(dá)水平呈顯著性正相關(guān)(r=0.996,P lt;0.01)。結(jié)論:p38MAPK對(duì)TNF-α生成的調(diào)節(jié)作用層次可能在轉(zhuǎn)錄水平,提示p38MAPK信號(hào)轉(zhuǎn)導(dǎo)途徑對(duì)TNF-α mRNA的調(diào)節(jié)可能是導(dǎo)致離體肝臟缺血再灌注損傷的重要機(jī)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(hào)轉(zhuǎn)導(dǎo)途徑對(duì)TNFα mRNA表達(dá)的影響. 華西醫(yī)學(xué), 2009, 24(6): 1475-1479. doi: 復(fù)制

1.
2.
3.
4.
5.
6.
7.
8. 王雨,田伏洲,湯禮軍,等.P38信號(hào)轉(zhuǎn)導(dǎo)途徑對(duì)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..
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. 冉江華,郭永章,李立,等.重組人生長(zhǎng)激素對(duì)大鼠肝臟缺血再灌注損傷的保護(hù)作用[J].中國(guó)普外基礎(chǔ)與臨床雜志,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. 簡(jiǎn)文,樊愛(ài)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(xué)機(jī)制的實(shí)驗(yàn)研究[J].第四軍醫(yī)大學(xué)學(xué)報(bào),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. 崔堯元,余勇,張曉彪,等.細(xì)胞間黏附分子1腫瘤壞死因子α轉(zhuǎn)錄水平在缺血再灌注大鼠腦皮質(zhì)中表達(dá)的相關(guān)性[J].中華實(shí)驗(yàn)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(duì)支氣管哮喘大鼠Th2類(lèi)細(xì)胞因子表達(dá)的調(diào)控[J].中國(guó)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(ài)華,張琳,等.脂多糖激活p38在誘導(dǎo)腫瘤壞死因子α基因表達(dá)中的作用[J].中華醫(yī)學(xué)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(duì)嚴(yán)重?zé)齻笫蟾闻K激活蛋白-1和核因子-κB的影響[J].中華損傷與修復(fù)雜志(電子版),2008,3(2):150..
24. 躍峰,李相成,姚愛(ài)華,等.缺血預(yù)處理對(duì)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(guó)普外基礎(chǔ)與臨床雜志,2006,13(5):531..
  1. 1.
  2. 2.
  3. 3.
  4. 4.
  5. 5.
  6. 6.
  7. 7.
  8. 8. 王雨,田伏洲,湯禮軍,等.P38信號(hào)轉(zhuǎn)導(dǎo)途徑對(duì)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..
  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(zhǎng)激素對(duì)大鼠肝臟缺血再灌注損傷的保護(hù)作用[J].中國(guó)普外基礎(chǔ)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(jiǎn)文,樊愛(ài)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(xué)機(jī)制的實(shí)驗(yàn)研究[J].第四軍醫(yī)大學(xué)學(xué)報(bào),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(xì)胞間黏附分子1腫瘤壞死因子α轉(zhuǎn)錄水平在缺血再灌注大鼠腦皮質(zhì)中表達(dá)的相關(guān)性[J].中華實(shí)驗(yàn)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(duì)支氣管哮喘大鼠Th2類(lèi)細(xì)胞因子表達(dá)的調(diào)控[J].中國(guó)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(ài)華,張琳,等.脂多糖激活p38在誘導(dǎo)腫瘤壞死因子α基因表達(dá)中的作用[J].中華醫(yī)學(xué)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(duì)嚴(yán)重?zé)齻笫蟾闻K激活蛋白-1和核因子-κB的影響[J].中華損傷與修復(fù)雜志(電子版),2008,3(2):150..
  24. 24. 躍峰,李相成,姚愛(ài)華,等.缺血預(yù)處理對(duì)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(guó)普外基礎(chǔ)與臨床雜志,2006,13(5):531..