Promoting Regeneration Effect of Heparin Binding Epidermal Growth Factor-Like Growth Factor on Rat Hepatocytes after Partial Orthotopic Liver Transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YANG Yan , LI Xiangcheng , WANG Xuehao , YAO Aihua , YU Yue

Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;

Corresponding author：

Keywords：

Liver transplantation; Liver regeneration; Heparin binding epidermal growth factor-like growth factor; Rat

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ObjectiveTo evaluate the effect of heparin binding epidermal growth factor-like growth factor (HB-EGF) on liver regeneration after partial orthotopic liver transplantation. MethodsFourty SD rats were used to establish the model of partial orthotopic liver transplantation with ameliorated two-cuff technique. Then all the rats were divided into 2 groups: experiment group and control group. Twenty rats of experiment group were administered 500 μg/kg HBEGF via vena caudalis immediately after operation twice a day, while the same volume of saline was administered to the rats in control group. Five rats in each group were selected randomly and killed at the 6th hour, day 2, 4 and 7 after operation, respectively. The serum levels of albumin (Alb) and alanine aminotransferase (ALT) in the blood sample were detected. Every liver was removed and weighed. The expression of Ki67 was detected by using immunohistochemistry assay. The regeneration activity of hepatocytes was evaluated by flow cytometry. ResultsThe wet weights of liver in experiment group were all significantly higher than that in control group at the 6th hour, day 2 and 4 after transplantation (P＜0.05). The serum levels of ALT were significantly lower in experiment group than those in control group at the 6th hour, day 2， 4, 7 after operation (P＜0.05), while the levels of Alb were significantly higher on day 4 and 7. The proliferating index and Ki-67 labeling index of graft in experiment group were higher than those in control group on day 2 and 4 after transplantation （2 d: P＜0.01; 4 d: P＜0.05）. ConclusionHBEGF could promote the regeneration of rat hepatocytes after partial liver transplantation.

Citation： YANG Yan,LI Xiangcheng,WANG Xuehao,YAO Aihua,YU Yue. Promoting Regeneration Effect of Heparin Binding Epidermal Growth Factor-Like Growth Factor on Rat Hepatocytes after Partial Orthotopic Liver Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(3): 155-158. doi: Copy

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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, 王学浩, 俞悦, 等. 大鼠肝移植后肝再生的实验研究 [J]. 中国普外基础与临床杂志, 2002； 9(4)∶228.

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. 彭方兴, 郑本波, 刘立新, 等. 大鼠原位肝移植动物模型制作要点 [J]. 中国普外基础与临床杂志， 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, 王学浩, 俞悦, 等. 大鼠肝移植后肝再生的实验研究 [J]. 中国普外基础与临床杂志, 2002； 9(4)∶228.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Promoting Regeneration Effect of Heparin Binding Epidermal Growth Factor-Like Growth Factor on Rat Hepatocytes after Partial Orthotopic Liver Transplantation

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