Study on Protection of Heme Oxygenase-1 in Rat Liver Transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Li ¹ , CHENG Li ¹ , LI Gengsheng ² , CUI Bin ³ , ZHANG Jin ⁴

1.Department of General Surgery;;
2.Department of Anesthesia;;
3.Institution Laboratory;;
4.Department of Pathology;;
Shandong Province Hospital, Jinan 250021, ChinaCorresponding Author： ZHANG Li， E-mail： pzzl@sina.com;

Corresponding author：

Keywords：

Heme oxygenase-1; Rat; Liver; Transplantation

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Objective 　To investigate the effect of heme oxygenase-1 (HO-1) activity on rat liver transplantation model.
Methods 　One hundred and thirty-seven rats were divided into 4 groups. Study control group (n＝44)： 24 h before operation, saline 5 ml/kg was infused into peritoneal cavity of donor rats; Hemin group (n＝44)： hemin 100 mg/kg was infused into peritoneal cavity of donor rats 24 h before operation, and hemin 100 mg/kg was infused into portal vein during the preserve time in 4 ℃ saline； ZnPP group (n＝44)： ZnPP 5 mg/kg was infused into peritoneal cavity of donor rats 24 h before operation, and ZnPP 5 mg/kg was infused into portal vein during the preserve time in 4 ℃ saline； Normal control group (n＝5)： normal rats as normal control group. Expressions of HO-1 protein and mRNA were detected with immunohistochemistry and RT-PCR technique respectively. The apoptosis rate of hepatocytes was analyzed by flow cytometry.
Results 　Expression of HO-1 mRNA in the liver of hemin group after transplantation was higher than that in study control group obviously, serum ALT and AST levels were lower than those in study control group (P＜0.05); HO-1 mRNA expression in ZnPP group liver was lower than that in study control group, serum ALT and AST levels were higher than those in study control group (P＜0.05). About liver cell apoptosis rate 48 h after liver transplantation, ZnPP group was the highest, hemin group was the minimum, and there had a significant difference between two groups (P＜0.05). Seven days after transplantation, the survival ratios of control study group, hemin group and ZnPP group were 7/12, 9/12 and 4/12 in turn, the inter-group differences had statistical significance (P＜0.05).
Conclusion 　Activity of HO-1 could be induced by the transplant operation. HO-1 increases the survival rate after liver transplantation which was related with reducing apoptotic ratio of hepatocyte and improve hepatic function.

Citation： ZHANG Li,CHENG Li,LI Gengsheng,CUI Bin,ZHANG Jin. Study on Protection of Heme Oxygenase-1 in Rat Liver Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(9): 665-670. doi: Copy

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13.	张黎，蒋进皎，杨镇, 等. 肝硬变门静脉高压症患者血红素氧化酶-1的表达 [Ｊ]. 中国普通外科杂志, 2003; 12(6)∶419.
14.	Rentsch M, Kienle K, Mueller T, et al. Adenoviral bcl-2 transfer improves survival and early graft function after ischemia and reperfusion in rat liver transplantation [Ｊ]. Transplantation, 2005; 80(10)∶1461.
15.	杜敦峰，昌盛，陈必成, 等. 血红素氧合酶-1抑制T淋巴细胞对血管内皮细胞的粘附作用 [Ｊ]. 中华器官移植杂志, 2005; 26(6)∶363.
16.	张中明，陈德海，董红燕, 等. 血红素氧化酶-1对紫绀型兔心脏复氧及缺血再灌注损伤的保护作用 [Ｊ]. 中华实验外科杂志，2005； 22(4)∶510.
17.	邵堂雷，蔡伟耀，杨伟平，等. 供肝冷热缺血移植后损伤与炎症细胞的关系 [Ｊ]. 中华肝脏病杂志, 2002; 10(6)∶455.
18.	Kato H, Amersi F, Buelow R, et al. Heme oxygenase-1 overexpression protects rat livers from ischemia/reperfusion injury with extended cold preservation [Ｊ]. Am J Transplant, 2001; 1(2)∶121.
19.	孟凡强，姜洪池，孙学英，等. 苦参素对大鼠肝缺血再灌注中肝细胞的保护作用及其机制探讨 [Ｊ]. 中华医学杂志, 2005; 85(28)∶1991.
20.	Katori M, Buelow R, Ke B, et al. Heme oxygenase-1 overexpression protects rat hearts from cold ischemia/reperfusion injury via an antiapoptotic pathway [Ｊ]. Transplantation, 2002; 73(2)∶287.
21.	Sato K, Balla J, Otterbein L, et al. Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants [Ｊ]. J Immunol, 2001; 166(6)∶4185.

1. 　Kamada N, Calne RY. A surgical experience with five hundred thirty liver transplants in the rat [Ｊ]. Surgery, 1983; 93 (1 Pt 1)∶64.
2. 　陈孝平主编. 外科常用实验方法及动物模型的建立 [M]. 第1版. 北京: 人民卫生出版社, 2003∶451~452.
3. 　Lu F, Zander DS, Visner GA. Increased expression of heme oxygenase-1 in human lung transplantation [Ｊ]. J Heart Lung Transplant, 2002; 21(10)∶1120.
4. 　Kobayashi T, Sato Y, Yamamoto S, et al. Augmentation of heme oxygenase-1 expression in the graft immediately after implantation in adult living-donor liver transplantation [Ｊ]. Transplantation, 2005; 79(8)∶977.
5. 　Yang ZF, Tsui TY, Ho DW, et al. Heme oxygenase-1 potentiates the survival of small-for-size liver graft [Ｊ]. Liver Transpl, 2004； 10(6)∶784.
6. 　Otterbein LE, Zukerbraun BS, Haga M, et al. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury [Ｊ]. Nat Med, 2003; 9(2)∶183.
7. 　Katori M, Busuttil RW, Kupiec-Weglinski JW. Heme oxygenase-1 system in organ transplantation [Ｊ]. Transplantation, 2002; 74(7)∶905.
8. 　王科，王学浩，张峰, 等. 诱导HO-1改善氧化应激状态减轻老年供肝缺血-再灌注损伤 [Ｊ]. 中国普外基础与临床杂志， 2005; 12(2)∶109.
9. 　马跃峰，李相成，姚爱华, 等. 缺血预处理对大鼠肝脏移植物再灌注早期NF-κB活性的影响及意义 [Ｊ]. 中国普外基础与临床杂志, 2006; 13(5)∶531.
10. 　Coito AJ, Buelow R, Shen XD, et al. Heme oxygenase-1 gene transfer inhibits inducible nitric oxide synthase expression and protects genetically fat Zucker rat livers from ischemia-reperfusion injury [Ｊ].Transplantation, 2002; 74(1)∶96.
11. 　丁纪明，陈平，张林, 等. 切应力对大鼠肝窦内皮细胞分泌功能的影响 [Ｊ]. 中国普外基础与临床杂志， 2005; 12(5)∶455.
12. 　张黎，黄加栋，杨镇, 等. 门静脉高压大鼠血红素氧化酶-1 mRNA的表达 [Ｊ]. 中国普通外科杂志, 2002; 11(9)∶551.
13. 　张黎，蒋进皎，杨镇, 等. 肝硬变门静脉高压症患者血红素氧化酶-1的表达 [Ｊ]. 中国普通外科杂志, 2003; 12(6)∶419.
14. 　Rentsch M, Kienle K, Mueller T, et al. Adenoviral bcl-2 transfer improves survival and early graft function after ischemia and reperfusion in rat liver transplantation [Ｊ]. Transplantation, 2005; 80(10)∶1461.
15. 　杜敦峰，昌盛，陈必成, 等. 血红素氧合酶-1抑制T淋巴细胞对血管内皮细胞的粘附作用 [Ｊ]. 中华器官移植杂志, 2005; 26(6)∶363.
16. 　张中明，陈德海，董红燕, 等. 血红素氧化酶-1对紫绀型兔心脏复氧及缺血再灌注损伤的保护作用 [Ｊ]. 中华实验外科杂志，2005； 22(4)∶510.
17. 　邵堂雷，蔡伟耀，杨伟平，等. 供肝冷热缺血移植后损伤与炎症细胞的关系 [Ｊ]. 中华肝脏病杂志, 2002; 10(6)∶455.
18. 　Kato H, Amersi F, Buelow R, et al. Heme oxygenase-1 overexpression protects rat livers from ischemia/reperfusion injury with extended cold preservation [Ｊ]. Am J Transplant, 2001; 1(2)∶121.
19. 　孟凡强，姜洪池，孙学英，等. 苦参素对大鼠肝缺血再灌注中肝细胞的保护作用及其机制探讨 [Ｊ]. 中华医学杂志, 2005; 85(28)∶1991.
20. 　Katori M, Buelow R, Ke B, et al. Heme oxygenase-1 overexpression protects rat hearts from cold ischemia/reperfusion injury via an antiapoptotic pathway [Ｊ]. Transplantation, 2002; 73(2)∶287.
21. 　Sato K, Balla J, Otterbein L, et al. Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants [Ｊ]. J Immunol, 2001; 166(6)∶4185.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study on Protection of Heme Oxygenase-1 in Rat Liver Transplantation

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