• 南京醫(yī)科大學(xué)第一附屬醫(yī)院肝臟移植中心（南京210029）;

目的:探討肝素結(jié)合的類表皮生長(zhǎng)因子(heparin binding epidermal growth factor-like growth factor, HB-EGF)對(duì)大鼠減體積肝移植術(shù)后肝細(xì)胞再生的促進(jìn)作用。方法:采用改良“二袖套法”建立大鼠原位減體積肝移植模型,分為實(shí)驗(yàn)組和對(duì)照組,術(shù)后即刻經(jīng)尾靜脈分別給予HB-EGF(500 μg/kg)和相同體積的生理鹽水,2次/d。2組分別在術(shù)后第6 h、2 d、4 d及7 d隨機(jī)挑取5只大鼠處死,稱取移植物濕重,采血檢測(cè)血清丙氨酸轉(zhuǎn)氨酶(ALT)及白蛋白(Alb),流式細(xì)胞儀檢測(cè)移植肝細(xì)胞的增殖活性,免疫組織化學(xué)法檢測(cè)移植肝Ki-67的表達(dá)情況。結(jié)果:術(shù)后第6 h、2 d和4 d,實(shí)驗(yàn)組移植物濕重較對(duì)照組相應(yīng)時(shí)相明顯增加（P＜0.05）; 術(shù)后第6 h、2 d、4 d和7 d,實(shí)驗(yàn)組血清ALT水平較對(duì)照組相應(yīng)時(shí)相明顯降低(P＜0.05),而第4和7d時(shí)Alb水平較對(duì)照組相應(yīng)時(shí)相明顯增高(P＜0.05);術(shù)后第2和4d時(shí),實(shí)驗(yàn)組的移植肝細(xì)胞增殖指數(shù)和Ki-67表達(dá)較對(duì)照組高（2d:P＜0.01; 4 d: P＜0.05。結(jié)論:大鼠原位減體積肝移植術(shù)后使用HB-EGF能夠明顯促進(jìn)移植肝細(xì)胞的再生。

引用本文： 楊焱,李相成,王學(xué)浩,姚愛華,俞悅. 肝素結(jié)合的類表皮生長(zhǎng)因子促進(jìn)大鼠減體積肝移植術(shù)后移植肝細(xì)胞的再生. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008, 15(3): 155-158. doi: 復(fù)制

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1. Nanba D, Kinugasa Y, Morimoto C, et al. Loss of HBEGF in smooth muscle or endothelial cell lineages causes heart malformation [J]. Biochem Biophys Res Commun, 2006; 350(2)∶315.
2. Shirakata Y, Kimura R, Nanba D, et al. Heparinbinding EGFlike growth factor accelerates keratinocyte migration and skin wound healing [J]. J Cell Sci, 2005; 118(Pt 11)∶2363.
3. Mine N, Iwamoto R, Mekada E. HBEGF promotes epithelial cell migration in eyelid development [J]. Development, 2005; 132(19)∶4317.
4. Xie H, Wang H, Tranguch S, et al. Maternal heparinbindingEGF deficiency limits pregnancy success in mice [J]. Proc Natl Acad Sci USA, 2007; 104(46)∶18315.
5. Clarke MC, Figg N, Maguire JJ, et al. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis [J]. Nat Med, 2006; 12(9)∶1075.
6. Ongusaha PP, Kwak JC, Zwible AJ, et al. HBEGF is a potent inducer of tumor growth and angiogenesis [J]. Cancer Res, 2004; 64(15)∶5283.
7. Kiso S, Kawata S, Tamura S, et al. Liver regeneration in heparinbinding EGFlike growth factor transgenic mice after partial hepatectomy [J]. Gastroenterology, 2003; 124(3)∶701.
8. 彭方興, 鄭本波, 劉立新, 等. 大鼠原位肝移植動(dòng)物模型制作要點(diǎn) [J]. 中國(guó)普外基礎(chǔ)與臨床雜志， 2005； 12（2）∶117.
9. Broelsch CE, Testa G, Alexandrou A, et al. Living related liver transplantation: medical and social aspects of a controversial therapy [J]. Gut, 2002; 50(2)∶143.
10. Broelsch CE, Burdelski M, Rogiers X, et al. Living donor for liver transplantation [J]. Hepatology, 1994; 20(1 Pt 2)∶49S.
11. Man K, Fan ST, Lo CM, et al. Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression [J]. Ann Surg, 2003; 237(2)∶256.
12. Man K, Lo CM, Ng IO, et al. Liver transplantation in rats using smallforsize grafts: a study of hemodynamic and morphological changes [J]. Arch Surg, 2001; 136(3)∶280.
13. Liang TB, Man K, KinWah Lee T, et al. Distinct intragraft response pattern in relation to graft size in liver transplantation [J]. Transplantation, 2003; 75(5)∶673.
14. Man K, Lo CM, Lee TK, et al. Intragraft gene expression profiles by cDNA microarray in smallforsize liver grafts [J]. Liver Transpl, 2003; 9(4)∶425.
15. Khai NC, Takahashi T, Ushikoshi H, et al. In vivo hepatic HBEGF gene transduction inhibits Fasinduced liver injury and induces liver regeneration in mice: a comparative study to HGF [J]. J Hepatol, 2006; 44(6)∶1046.
16. Khandoga A, Biberthaler P, Enders G, et al. Pselectin mediates plateletendothelial cell interactions and reperfusion injury in the mouse liver in vivo [J]. Shock, 2002; 18(6)∶529.
17. Rocourt DV, Mehta VB, Besner GE. Heparinbinding EGFlike growth factor decreases inflammatory cytokine expression after intestinal ischemia/reperfusion injury [J]. J Surg Res, 2007; 139(2)∶269.
18. Shimizu H, Miyazaki M, Ito H, et al. Mechanism of cold ischemiareperfusioninduced graft injury after orthotopic liver transplantation in rats [J]. Hepatogastroenterology, 2001; 48(37)∶216.
19. Wang J, Tahara K, Hakamata Y, et al. Auxiliary partial liver grafting in rats: effect of host hepatectomy on graft regeneration, and review of literature on surgical technique [J]. Microsurgery, 2002; 22(8)∶371.
20. 李相成, 王學(xué)浩, 俞悅, 等. 大鼠肝移植后肝再生的實(shí)驗(yàn)研究 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2002； 9(4)∶228.
  1. 1. Nanba D, Kinugasa Y, Morimoto C, et al. Loss of HBEGF in smooth muscle or endothelial cell lineages causes heart malformation [J]. Biochem Biophys Res Commun, 2006; 350(2)∶315.
  2. 2. Shirakata Y, Kimura R, Nanba D, et al. Heparinbinding EGFlike growth factor accelerates keratinocyte migration and skin wound healing [J]. J Cell Sci, 2005; 118(Pt 11)∶2363.
  3. 3. Mine N, Iwamoto R, Mekada E. HBEGF promotes epithelial cell migration in eyelid development [J]. Development, 2005; 132(19)∶4317.
  4. 4. Xie H, Wang H, Tranguch S, et al. Maternal heparinbindingEGF deficiency limits pregnancy success in mice [J]. Proc Natl Acad Sci USA, 2007; 104(46)∶18315.
  5. 5. Clarke MC, Figg N, Maguire JJ, et al. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis [J]. Nat Med, 2006; 12(9)∶1075.
  6. 6. Ongusaha PP, Kwak JC, Zwible AJ, et al. HBEGF is a potent inducer of tumor growth and angiogenesis [J]. Cancer Res, 2004; 64(15)∶5283.
  7. 7. Kiso S, Kawata S, Tamura S, et al. Liver regeneration in heparinbinding EGFlike growth factor transgenic mice after partial hepatectomy [J]. Gastroenterology, 2003; 124(3)∶701.
  8. 8. 彭方興, 鄭本波, 劉立新, 等. 大鼠原位肝移植動(dòng)物模型制作要點(diǎn) [J]. 中國(guó)普外基礎(chǔ)與臨床雜志， 2005； 12（2）∶117.
  9. 9. Broelsch CE, Testa G, Alexandrou A, et al. Living related liver transplantation: medical and social aspects of a controversial therapy [J]. Gut, 2002; 50(2)∶143.
  10. 10. Broelsch CE, Burdelski M, Rogiers X, et al. Living donor for liver transplantation [J]. Hepatology, 1994; 20(1 Pt 2)∶49S.
  11. 11. Man K, Fan ST, Lo CM, et al. Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression [J]. Ann Surg, 2003; 237(2)∶256.
  12. 12. Man K, Lo CM, Ng IO, et al. Liver transplantation in rats using smallforsize grafts: a study of hemodynamic and morphological changes [J]. Arch Surg, 2001; 136(3)∶280.
  13. 13. Liang TB, Man K, KinWah Lee T, et al. Distinct intragraft response pattern in relation to graft size in liver transplantation [J]. Transplantation, 2003; 75(5)∶673.
  14. 14. Man K, Lo CM, Lee TK, et al. Intragraft gene expression profiles by cDNA microarray in smallforsize liver grafts [J]. Liver Transpl, 2003; 9(4)∶425.
  15. 15. Khai NC, Takahashi T, Ushikoshi H, et al. In vivo hepatic HBEGF gene transduction inhibits Fasinduced liver injury and induces liver regeneration in mice: a comparative study to HGF [J]. J Hepatol, 2006; 44(6)∶1046.
  16. 16. Khandoga A, Biberthaler P, Enders G, et al. Pselectin mediates plateletendothelial cell interactions and reperfusion injury in the mouse liver in vivo [J]. Shock, 2002; 18(6)∶529.
  17. 17. Rocourt DV, Mehta VB, Besner GE. Heparinbinding EGFlike growth factor decreases inflammatory cytokine expression after intestinal ischemia/reperfusion injury [J]. J Surg Res, 2007; 139(2)∶269.
  18. 18. Shimizu H, Miyazaki M, Ito H, et al. Mechanism of cold ischemiareperfusioninduced graft injury after orthotopic liver transplantation in rats [J]. Hepatogastroenterology, 2001; 48(37)∶216.
  19. 19. Wang J, Tahara K, Hakamata Y, et al. Auxiliary partial liver grafting in rats: effect of host hepatectomy on graft regeneration, and review of literature on surgical technique [J]. Microsurgery, 2002; 22(8)∶371.
  20. 20. 李相成, 王學(xué)浩, 俞悅, 等. 大鼠肝移植后肝再生的實(shí)驗(yàn)研究 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2002； 9(4)∶228.