• 1.蘭州軍區(qū)烏魯木齊總醫(yī)院普外科(烏魯木齊830000);;
  • 2.新鄉(xiāng)醫(yī)學(xué)院第一附屬醫(yī)院普外科(河南衛(wèi)輝453100);

目的 　探討核因子κB(NF-κB)在各種形式肝損傷發(fā)生、發(fā)展中的作用。
方法 　對近年來有關(guān)NF-κB結(jié)構(gòu)、分子生物學(xué)特性和功能及其與肝損傷關(guān)系方面的文章進(jìn)行綜述。
結(jié)果 　NF-κB是一種重要的核轉(zhuǎn)錄因子，廣泛存在于機(jī)體各種細(xì)胞中。在各種原因引起肝損傷時(shí)它可被誘導(dǎo)活化，活化的NF-κB可通過對細(xì)胞因子、黏附因子和活化因子轉(zhuǎn)錄活性的調(diào)節(jié)影響免疫反應(yīng)、炎癥反應(yīng)及細(xì)胞凋亡，從而參與肝損傷。
結(jié)論 　NF-κB在肝損傷的發(fā)生、發(fā)展中起重要作用，將成為肝損傷治療的新靶點(diǎn)。

引用本文： 林海,李澤信,劉江偉,張永久. 核因子-κB與肝損傷. 中國普外基礎(chǔ)與臨床雜志, 2007, 14(6): 731-734. doi: 復(fù)制

1. 　Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences [J]. Cell， 1986； 46（5）∶705.
2. 　Heyninck K, Wullaert A, Beyaert R. Nuclear factor-kappa B plays a central role in tumour necrosis factor-mediated liver disease [J]. Biochem Pharmacol， 2003; 66(8)∶1409.
3. 　Chen F, Shi X. NF-kappa B, a pivotal transcription factor in silica-induced diseases [J]. Mol Cell Biochem， 2002; 234-235(1-2)∶169.
4. 　Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-κB activity [J]. Annu Rev Immunol， 2000; 18∶621.
5. 　Storz P, Toker A. NF-kappaB signaling——an alternate pathway for oxidative stress responses [J]. Cell Cycle， 2003; 2(1)∶9.
6. 　Garg A, Aggarwal BB. Nuclear transcription factor-kappa B as a target for cancer drug development [J]. Leukemia， 2002; 16(6)∶1053.
7. 　Bowie A, O’Neill LA. Oxidative stress and nuclear factor-kappa B activation: a reassessment of the evidence in the light of recent discoveries [J]. Biochem Pharmacol， 2000; 59(1)∶13.
8. 　Ye J, Ding M, Zhang X, et al. On the role of hydroxyl radical and the effect of tetrandrine on nuclear factor-kappa B activation by phorbol 12-myristate 13-acetate [J]. Ann Clin Lab Sci， 2000; 30(1)∶65.
9. 　Mason NJ, Artis D, Hunter CA. New lessons from old pathogens: what parasitic infections have taught us about the role of nuclear factor-kappa B in the regulation of immunity [J]. Immunol Rev， 2004; 201（1）∶48.
10. 　Goebeler M, Gillitzer R, Kilian K, et al. Multiple signaling pathways regulate NF-kappa B-dependent transcription of the monocyte chemoattractant protein-1 gene in primary endothelial cells [J]. Blood， 2001; 97(1)∶46.
11. 　Aggarwal BB. Nuclear factor-kappa B: the enemy within [J]. Cancer Cell， 2004; 6(3)∶203.
12. 　Huber MA, Azoitei N, Baumann B, et al. NF-kappa B is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression [J]. J Clin Invest， 2004; 114(4)∶569.
13. 　Nanji AA, Jokelainen K, Rahemtulla A, et al. Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat [J]. Hepatology， 1999; 30(4)∶934.
14. 　Zwacka RM, Zhang Y, Zhou W, et al. Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor kappa B independently of I kappa B degradation [J]. Hepatology， 1998; 28(4)∶1022.
15. 　Fukuma K, Marubayashi S, Okada K, et al. Effect of lazaroid U-74389G and methylprednisolone on endotoxin-induced shock in mice [J]. Surgery， 1999; 125(4)∶421.
16. 　Harry D, Anand R, Holt S, et al. Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic Rat [J]. Hepatology， 1999; 30(5)∶1198.
17. 　Murr MM, Yang J, Fier A, et al. Pancreatic elastase induces liver injury by activating cytokine production within Kupffer cells via nuclear factor-Kappa B [J]. J Gastrointest Surg， 2002; 6(3)∶474.
18. 　馬躍峰， 李相成， 姚愛華， 等. 缺血預(yù)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(chǔ)與臨床雜志, 2006; 13(5)∶531.
19. 　楊文軍， 梁華平， 徐祥， 等. 核因子-κB靶向性寡核苷酸“圈套”策略對創(chuàng)傷性炎癥大鼠肝臟TNF-α的作用 [J]. 中華肝膽外科雜志， 2004; 10（3）∶177.
20. 　尹會男， 柴家科， 姚詠明， 等. NF-κB在燒傷膿毒癥大鼠肝損傷中的作用 [J]. 解放軍醫(yī)學(xué)雜志， 2004; 29（1）∶36.
21. 　王明海， 太光平， 張雅萍， 等. 重組腺病毒對燙傷大鼠肝組織核因子-κB活性的調(diào)控 [J]. 中華燒傷雜志， 2002; 18（1）∶42.
22. 　Kono H, Wheeler MD, Rusyn I, et al. Gender differences in early alcohol-induced liver injury: role of CD14, NF-kappa B, and TNF-alpha [J]. Am J Physiol Gastrointest Liver Physiol， 2000; 278(4)∶G652.
23. 　Essani NA, Fisher MA, Jaeschke H. Inhibition of NF-kappa B activation by dimethyl sulfoxide correlates with suppression of TNF-alpha formation, reduced ICAM-1 gene transcription, and protection against endotoxin-induced liver injury [J]. Shock， 1997; 7(2)∶90.
24. 　李躍華, 朱麗, 哈團(tuán)柱, 等. 刀豆素A誘導(dǎo)小鼠肝損傷增加肝臟NF-κB活性 [J]. 中華肝臟病雜志， 2003； 11（2）∶115.
25. 　趙宗豪， 高人燾. 核因子κB與肝纖維化的研究進(jìn)展 [J]. 實(shí)用肝臟病雜志， 2004； 7（2）∶119.
26. 　Taub R. Liver regeneration 4: transcriptional control of liver regeneration [J]. FASEB J， 1996; 10(4)∶413.
27. 　Beg AA, Sha WC, Bronson RT, et al. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B [J]. Nature， 1995; 376(6536)∶167.
28. 　Schoemaker MH, Ros JE, Homan M, et al. Cytokine regulation of pro- and anti-apoptotic genes in rat hepatocytes: NF-kappa B-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis [J]. J Hepatol， 2002; 36(6)∶742.
29. 　Franek WR, Horowitz S, Stansberry L, et al. Hyperoxia inhibits oxidant-induced apoptosis in lung epithelial cells [J]. J Biol Chem， 2001; 276(1)∶569.
30. 　Grisham MB. NF-kappa B activation in acute pancreatitis: protective, detrimental, or inconsequential? [J]. Gastroenterology， 1999; 116(2)∶489.
31. 　Rakonczay Z Jr, Jarmay K, Kaszaki J, et al. NF-kappa B activation is detrimental in arginine-induced acute pancreatitis [J]. Free Radic Biol Med， 2003; 34(6)∶696.
32. 　Perkins ND. The Rel/NF-kappa B family: friend and foe [J]. Trends Biochem Sci， 2000; 25(9)∶434.
33. 　Virlos I, Mazzon E, Serraino I, et al. Calpain I inhibitor ameliorates the indices of disease severity in a murine model of cerulein-induced acute pancreatitis [J]. Intensive Care Med, 2004; 30(8)∶1645.
  1. 1. 　Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences [J]. Cell， 1986； 46（5）∶705.
  2. 2. 　Heyninck K, Wullaert A, Beyaert R. Nuclear factor-kappa B plays a central role in tumour necrosis factor-mediated liver disease [J]. Biochem Pharmacol， 2003; 66(8)∶1409.
  3. 3. 　Chen F, Shi X. NF-kappa B, a pivotal transcription factor in silica-induced diseases [J]. Mol Cell Biochem， 2002; 234-235(1-2)∶169.
  4. 4. 　Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-κB activity [J]. Annu Rev Immunol， 2000; 18∶621.
  5. 5. 　Storz P, Toker A. NF-kappaB signaling——an alternate pathway for oxidative stress responses [J]. Cell Cycle， 2003; 2(1)∶9.
  6. 6. 　Garg A, Aggarwal BB. Nuclear transcription factor-kappa B as a target for cancer drug development [J]. Leukemia， 2002; 16(6)∶1053.
  7. 7. 　Bowie A, O’Neill LA. Oxidative stress and nuclear factor-kappa B activation: a reassessment of the evidence in the light of recent discoveries [J]. Biochem Pharmacol， 2000; 59(1)∶13.
  8. 8. 　Ye J, Ding M, Zhang X, et al. On the role of hydroxyl radical and the effect of tetrandrine on nuclear factor-kappa B activation by phorbol 12-myristate 13-acetate [J]. Ann Clin Lab Sci， 2000; 30(1)∶65.
  9. 9. 　Mason NJ, Artis D, Hunter CA. New lessons from old pathogens: what parasitic infections have taught us about the role of nuclear factor-kappa B in the regulation of immunity [J]. Immunol Rev， 2004; 201（1）∶48.
  10. 10. 　Goebeler M, Gillitzer R, Kilian K, et al. Multiple signaling pathways regulate NF-kappa B-dependent transcription of the monocyte chemoattractant protein-1 gene in primary endothelial cells [J]. Blood， 2001; 97(1)∶46.
  11. 11. 　Aggarwal BB. Nuclear factor-kappa B: the enemy within [J]. Cancer Cell， 2004; 6(3)∶203.
  12. 12. 　Huber MA, Azoitei N, Baumann B, et al. NF-kappa B is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression [J]. J Clin Invest， 2004; 114(4)∶569.
  13. 13. 　Nanji AA, Jokelainen K, Rahemtulla A, et al. Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat [J]. Hepatology， 1999; 30(4)∶934.
  14. 14. 　Zwacka RM, Zhang Y, Zhou W, et al. Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor kappa B independently of I kappa B degradation [J]. Hepatology， 1998; 28(4)∶1022.
  15. 15. 　Fukuma K, Marubayashi S, Okada K, et al. Effect of lazaroid U-74389G and methylprednisolone on endotoxin-induced shock in mice [J]. Surgery， 1999; 125(4)∶421.
  16. 16. 　Harry D, Anand R, Holt S, et al. Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic Rat [J]. Hepatology， 1999; 30(5)∶1198.
  17. 17. 　Murr MM, Yang J, Fier A, et al. Pancreatic elastase induces liver injury by activating cytokine production within Kupffer cells via nuclear factor-Kappa B [J]. J Gastrointest Surg， 2002; 6(3)∶474.
  18. 18. 　馬躍峰， 李相成， 姚愛華， 等. 缺血預(yù)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(chǔ)與臨床雜志, 2006; 13(5)∶531.
  19. 19. 　楊文軍， 梁華平， 徐祥， 等. 核因子-κB靶向性寡核苷酸“圈套”策略對創(chuàng)傷性炎癥大鼠肝臟TNF-α的作用 [J]. 中華肝膽外科雜志， 2004; 10（3）∶177.
  20. 20. 　尹會男， 柴家科， 姚詠明， 等. NF-κB在燒傷膿毒癥大鼠肝損傷中的作用 [J]. 解放軍醫(yī)學(xué)雜志， 2004; 29（1）∶36.
  21. 21. 　王明海， 太光平， 張雅萍， 等. 重組腺病毒對燙傷大鼠肝組織核因子-κB活性的調(diào)控 [J]. 中華燒傷雜志， 2002; 18（1）∶42.
  22. 22. 　Kono H, Wheeler MD, Rusyn I, et al. Gender differences in early alcohol-induced liver injury: role of CD14, NF-kappa B, and TNF-alpha [J]. Am J Physiol Gastrointest Liver Physiol， 2000; 278(4)∶G652.
  23. 23. 　Essani NA, Fisher MA, Jaeschke H. Inhibition of NF-kappa B activation by dimethyl sulfoxide correlates with suppression of TNF-alpha formation, reduced ICAM-1 gene transcription, and protection against endotoxin-induced liver injury [J]. Shock， 1997; 7(2)∶90.
  24. 24. 　李躍華, 朱麗, 哈團(tuán)柱, 等. 刀豆素A誘導(dǎo)小鼠肝損傷增加肝臟NF-κB活性 [J]. 中華肝臟病雜志， 2003； 11（2）∶115.
  25. 25. 　趙宗豪， 高人燾. 核因子κB與肝纖維化的研究進(jìn)展 [J]. 實(shí)用肝臟病雜志， 2004； 7（2）∶119.
  26. 26. 　Taub R. Liver regeneration 4: transcriptional control of liver regeneration [J]. FASEB J， 1996; 10(4)∶413.
  27. 27. 　Beg AA, Sha WC, Bronson RT, et al. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B [J]. Nature， 1995; 376(6536)∶167.
  28. 28. 　Schoemaker MH, Ros JE, Homan M, et al. Cytokine regulation of pro- and anti-apoptotic genes in rat hepatocytes: NF-kappa B-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis [J]. J Hepatol， 2002; 36(6)∶742.
  29. 29. 　Franek WR, Horowitz S, Stansberry L, et al. Hyperoxia inhibits oxidant-induced apoptosis in lung epithelial cells [J]. J Biol Chem， 2001; 276(1)∶569.
  30. 30. 　Grisham MB. NF-kappa B activation in acute pancreatitis: protective, detrimental, or inconsequential? [J]. Gastroenterology， 1999; 116(2)∶489.
  31. 31. 　Rakonczay Z Jr, Jarmay K, Kaszaki J, et al. NF-kappa B activation is detrimental in arginine-induced acute pancreatitis [J]. Free Radic Biol Med， 2003; 34(6)∶696.
  32. 32. 　Perkins ND. The Rel/NF-kappa B family: friend and foe [J]. Trends Biochem Sci， 2000; 25(9)∶434.
  33. 33. 　Virlos I, Mazzon E, Serraino I, et al. Calpain I inhibitor ameliorates the indices of disease severity in a murine model of cerulein-induced acute pancreatitis [J]. Intensive Care Med, 2004; 30(8)∶1645.