血红素加氧酶-1对大鼠肝移植术后肝脏保护作用的研究
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摘要
目的：利用套管技术建立稳定的大鼠原位肝移植动物模型，模型的建立是本项研究的基础。
方法：采用“二袖套法”完成200例次大鼠原位肝移植模型，同时结合自己的体会，对“二袖套法”进行适当改进，包括套管的制作、受体的麻醉、腹主动脉的灌注以及肝上、肝下下腔静脉、门静脉等血管的吻合。
结果：肝上下腔静脉的吻合时间为10～15分钟，无肝期为12～18分钟，一周生存率可达75％以上。术后常见的并发症为出血、血栓形成、感染以及胆道梗阻。
结论：技术的改进增加了生存率，包括供肝腹主动脉灌注，在供肝的质量上明显优于单纯门静脉灌注。另外，减少供肝的机械性损伤、避免套管的扭曲、提高血管的吻合质量以及缩短无肝期，都是减少术后并发症和提高移植物存活的关键。
目的：1．构建Ad-HO-1重组腺病毒载体，并鉴定其安全性及生物活性。
方法与结果：1．Ad-HO-1重组腺病毒载体的构建及鉴定用限制性内切酶XhoⅠ+HindⅢ从克隆载体PRH01中切出HO-1基因片段，亚克隆至经SalⅠ+HindⅢ酶切的克隆质粒Puc18中，形成转移质粒Puc18-PRH01，将之用KpnⅠ+HindⅢ双酶切，再次亚克隆至经同样酶切的质粒pAdTrack-CMV中，形成转移质粒pAdTrack-Puc18-PRHO1，将之PmeⅠ酶切线性化后与腺病毒基因组质粒pAdEasy-1共转化大肠杆菌BJ5183，在BJ5183菌种中进行同源重组，得到腺病毒质粒pAdEasy-HO-1，经293细胞包装后，扩增、浓缩，最终获得高效、稳定、安全表达HO-1基因腺病毒Ad-HO-1。通过PCR、基因测序进行鉴定。
结论：1．采用DNA重组技术，成功构建了重组腺病毒Ad-HO-1；2．经PCR、荧光显微镜等检测表明：重组腺病毒Ad-HO-1能高效、稳定的表达HO-1目的基因和具有良好的安全性；
目的：以近交系大鼠肝移植模型为基础，研究HO-1基因转染对移植肝的保护作用。
方法与结果：以近交系大鼠肝移植模型为基础，将重组HO-1／Ad感染移植肝，观察大鼠的生存情况、检测肝脏功能、观察HO-1在肝脏的表达及肝脏病理改变。发现肝外器官中没有转染的HO-1基因表达；HO-1在肝脏组织中的表达与G4组大鼠生存时间延长、肝功能变化、肝脏组织中淋巴细胞浸润时间滞后、数量减少及肝组织的破坏程度呈相关。
结论：HO-1对移植肝有保护作用，可延长其存活时间，具有潜在的临床应用价值。
Objectives: To establish a rat model of stable orthtopic livertransplantation(OLT)using cuff technique, the establishment of a rat OLTis the precondition to perform such study.
Methods: OLT in 200 SD rats which received Wistar liver wereestablished by using "the two-cuff technique" with some modification incuff tube, recipients anesthesia abdominal aorta perfusion and theanastomosis of suprahepatic vena cava, portal vein, infrahepatic venacava.
Results:The time of vascular anastomosis for suprahepatic venacava was 10 to 15 minutes, the anhepatic phase was 12 to 18 minutes,more than 75％of the grafted animals survived for seven days. Bleeding,thrombosis, infection and biliary obstruction
Objective: To construct and identify HO-1 gene recombinantreplication-deficient adenovirus(Ad-HO-1).
Methods and Results: The construction and identification of HO-1gene recombinant replication deficient adenovirus.In this study, we usedAdEasy system to construct HO-1 recombinant replication-deficientadenovirus. Firstly, the whole HO-1 gene was obtained from the PRHO-1plasmid via XhoⅠ+HindⅢdigestion, and inserted into Pucl8 plasmid.Then HO-1 gene was digested from Puc 18-HO-1 by KpnⅠ+HindⅢandsubcloned into shuttle vector of pAdTrack-CMV. The resulting plasmidpAdTrack-CMV-HO-1 was linearized with PmeⅠand cotransformedinto BJ5183 cells together with adenovirus genomic plasmid ofpAdEasy-1. The pAdEasy-1 was E1 and E3 deleted and its E1 functioncould be complemented in 293 cells. Recombinants were selected withkanamycin and screened by restriction enzyme analysis. The recombinantadenoviral construct was then cleaved with PacI to expose its ITR(Inverted Terminal Repeats) and transfected 293 cells to produce viralparticles. Recombinant adenoviruse was purified by Double CesiumChloride Gradient and titered (infectious particles, IP) as TCID50 (tissueculture infectious dose 50).Adenovirus stocks were tested for the absence of replication-competent adenoviruses by PCR amplification of the E1adenoviral region. The resulting recombinant adenovirus was identifiedby PCR of HO-1 gene and expression of HO-1 protein by western blot.
Conclusion: HO-1 gene recombinant replication-deficientadenovirus was successfully constructed.2.HO-1 gene recombinantreplication-deficient adenovirus had the qualities of high efficiency, stableexpression of HO-1 and safety in cultured tubular epithelial cells.
Objective: To investigate the protected effects of HO-1 genetransfection on liver allografts based on rat allograft model.
Methods and Results: we established inbred rat livertransplantation model and infected liver allograft with recombinantHO-1/Ad. Then we observed the survival time, HO-1 expression andpathological changes in liver allograft, and measured the changes ofhepatic function. The results indicate that HO-1 expression is correlatedwith the changes of hepatic function, delayed lymphocytes infiltration,decreased number of lymphocytes infiltrated into liver aUograft and mildpathological changes in liver allograft. There is no expression oftransfected HO-1 gene in the other organs all the time.
Conclusion: HO-1 can protect liver allograft from graft rejectionand prolong the survival time of liver alloRraft, so it has a therapeuticpotential in graft rejection.
方法：采用“二袖套法”完成200例次大鼠原位肝移植模型，同时结合自己的体会，对“二袖套法”进行适当改进，包括套管的制作、受体的麻醉、腹主动脉的灌注以及肝上、肝下下腔静脉、门静脉等血管的吻合。
结果：肝上下腔静脉的吻合时间为10～15分钟，无肝期为12～18分钟，一周生存率可达75％以上。术后常见的并发症为出血、血栓形成、感染以及胆道梗阻。
结论：技术的改进增加了生存率，包括供肝腹主动脉灌注，在供肝的质量上明显优于单纯门静脉灌注。另外，减少供肝的机械性损伤、避免套管的扭曲、提高血管的吻合质量以及缩短无肝期，都是减少术后并发症和提高移植物存活的关键。
目的：1．构建Ad-HO-1重组腺病毒载体，并鉴定其安全性及生物活性。
方法与结果：1．Ad-HO-1重组腺病毒载体的构建及鉴定用限制性内切酶XhoⅠ+HindⅢ从克隆载体PRH01中切出HO-1基因片段，亚克隆至经SalⅠ+HindⅢ酶切的克隆质粒Puc18中，形成转移质粒Puc18-PRH01，将之用KpnⅠ+HindⅢ双酶切，再次亚克隆至经同样酶切的质粒pAdTrack-CMV中，形成转移质粒pAdTrack-Puc18-PRHO1，将之PmeⅠ酶切线性化后与腺病毒基因组质粒pAdEasy-1共转化大肠杆菌BJ5183，在BJ5183菌种中进行同源重组，得到腺病毒质粒pAdEasy-HO-1，经293细胞包装后，扩增、浓缩，最终获得高效、稳定、安全表达HO-1基因腺病毒Ad-HO-1。通过PCR、基因测序进行鉴定。
结论：1．采用DNA重组技术，成功构建了重组腺病毒Ad-HO-1；2．经PCR、荧光显微镜等检测表明：重组腺病毒Ad-HO-1能高效、稳定的表达HO-1目的基因和具有良好的安全性；
目的：以近交系大鼠肝移植模型为基础，研究HO-1基因转染对移植肝的保护作用。
方法与结果：以近交系大鼠肝移植模型为基础，将重组HO-1／Ad感染移植肝，观察大鼠的生存情况、检测肝脏功能、观察HO-1在肝脏的表达及肝脏病理改变。发现肝外器官中没有转染的HO-1基因表达；HO-1在肝脏组织中的表达与G4组大鼠生存时间延长、肝功能变化、肝脏组织中淋巴细胞浸润时间滞后、数量减少及肝组织的破坏程度呈相关。
结论：HO-1对移植肝有保护作用，可延长其存活时间，具有潜在的临床应用价值。
Objectives: To establish a rat model of stable orthtopic livertransplantation(OLT)using cuff technique, the establishment of a rat OLTis the precondition to perform such study.
Methods: OLT in 200 SD rats which received Wistar liver wereestablished by using "the two-cuff technique" with some modification incuff tube, recipients anesthesia abdominal aorta perfusion and theanastomosis of suprahepatic vena cava, portal vein, infrahepatic venacava.
Results:The time of vascular anastomosis for suprahepatic venacava was 10 to 15 minutes, the anhepatic phase was 12 to 18 minutes,more than 75％of the grafted animals survived for seven days. Bleeding,thrombosis, infection and biliary obstruction
Objective: To construct and identify HO-1 gene recombinantreplication-deficient adenovirus(Ad-HO-1).
Methods and Results: The construction and identification of HO-1gene recombinant replication deficient adenovirus.In this study, we usedAdEasy system to construct HO-1 recombinant replication-deficientadenovirus. Firstly, the whole HO-1 gene was obtained from the PRHO-1plasmid via XhoⅠ+HindⅢdigestion, and inserted into Pucl8 plasmid.Then HO-1 gene was digested from Puc 18-HO-1 by KpnⅠ+HindⅢandsubcloned into shuttle vector of pAdTrack-CMV. The resulting plasmidpAdTrack-CMV-HO-1 was linearized with PmeⅠand cotransformedinto BJ5183 cells together with adenovirus genomic plasmid ofpAdEasy-1. The pAdEasy-1 was E1 and E3 deleted and its E1 functioncould be complemented in 293 cells. Recombinants were selected withkanamycin and screened by restriction enzyme analysis. The recombinantadenoviral construct was then cleaved with PacI to expose its ITR(Inverted Terminal Repeats) and transfected 293 cells to produce viralparticles. Recombinant adenoviruse was purified by Double CesiumChloride Gradient and titered (infectious particles, IP) as TCID50 (tissueculture infectious dose 50).Adenovirus stocks were tested for the absence of replication-competent adenoviruses by PCR amplification of the E1adenoviral region. The resulting recombinant adenovirus was identifiedby PCR of HO-1 gene and expression of HO-1 protein by western blot.
Conclusion: HO-1 gene recombinant replication-deficientadenovirus was successfully constructed.2.HO-1 gene recombinantreplication-deficient adenovirus had the qualities of high efficiency, stableexpression of HO-1 and safety in cultured tubular epithelial cells.
Objective: To investigate the protected effects of HO-1 genetransfection on liver allografts based on rat allograft model.
Methods and Results: we established inbred rat livertransplantation model and infected liver allograft with recombinantHO-1/Ad. Then we observed the survival time, HO-1 expression andpathological changes in liver allograft, and measured the changes ofhepatic function. The results indicate that HO-1 expression is correlatedwith the changes of hepatic function, delayed lymphocytes infiltration,decreased number of lymphocytes infiltrated into liver aUograft and mildpathological changes in liver allograft. There is no expression oftransfected HO-1 gene in the other organs all the time.
Conclusion: HO-1 can protect liver allograft from graft rejectionand prolong the survival time of liver alloRraft, so it has a therapeuticpotential in graft rejection.
引文
[1] Kamada N, Calne R. A surgical experience with five hundred thirty liver transplantation in the rat. Surgery, 1983, 93: 64
[2] 郑树森主编．肝脏移植．北京：人民卫生出版社，2001．139
[3] Miyata M, Fisher J, Fuhs M, et al. A simple method for orthotopic liver transplantation in the rat. Transplantation, 1980, 30: 335～338
[4] Kobayashi E, Kamada N, Goto S, et al. Protocol for the techinique of orthotopic liver transplantation in the rot. Microsurgery, 1993, 14: 541～546
[5] Delriviere L, Gibbs P, Kobayashi E, et al. Detailed modified technique for safer harvesting and preparation of liver graft in the rat. Microsurgery, 1996, 17(12): 690～696
[6] Schemmer P, Schoonhoven R, Swenberg JA, et al. Gental in situ liver manipulation during organ harvest decreases survival after rat liver transplantation. Role of Kupffer cells. Transplantation, 1998, 42: 330～331
[7] Tokunaga Y, Ozaki N, Wakashiro S, et al. Effects of perfusion pressure during plushing on the viability of the procured liver using noninvasive fluorometry. Transplantation, 1988, 45: 1031
[8] Marni A, Ferrero ME, Forti D, et al. Advantages of cuff techniques versus standard microsurgical techniques in heterotopic nonauxiliary liver transplantation in rats. Transplant Proc, 1987, 91: 3854～3858
[9] Delrivjete L, Gibbs P, Kobayashi E, et al. Technical details for safer venous and biliary anastomoses for liver transplantation in the rat. Microsurgery, 1998, 19(1): 12～18
[10] 王轩，扬甲梅，严以群，等．大鼠原位肝移植不同术式的探讨．中华器官移植杂志，1998，19(2)：76～78
[11] Kamada N, Calne RY. Orthotopic liver transplantation in the rat: technique technique using cuff for portal vein anastomosis and biliary drinage. Transplantation, 1979, 28: 47～49
[12] Goto M, Takei Y, Kawanno S, et al. Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in rat. Hepatology, 1992, 16: 487
[13] Meyer K, Brown MF, Zibari G, et al. ICAM-1 upregulation in distant tissue after hepatic ischemia/reperfusion: a clue to the mechanism of multiple organ failure. J Pediatr Surg, 1998, 33: 350
[14] 孙君泓，吴孟超，曾琪华．300次大鼠原位肝移植．中华器官移植杂志，1990，11：19～21
[15] 张文海，有井滋村，董雨亭．等．大鼠原位肝移植术并发症的预防．中华器官移植杂志，1995，16：12～14
[1] Kelly VR and Sukhatme VP. Gene transfer in the kidney[J]. Am J Physiol.1999,276(1Pt2):F1-9.
[2] Hart DN, Newton MR, Reece-Smith H, et al. Major histoeompatibility complex antigens in the rat pancreas, isolated pancreatic islets, thyroid, and adrenal [J].Transplantation. 1983,36(4): 431-435.
[3] Hart DN and Fabre JW. Mechanism of induction of passive enhancement. Evidence for an interaction of enhancing antibody with donor interstitial dendritic eells[J]. Transplantation. 1982, 33(3): 319-322.
[4] Karl A. Nath. Heme oxygenase-1: a redoubtable response that limits reperfusion injury in the transplanted adipose live. J. Clin. Invest, 1999, 1485-1486.
[5] Lim FY, Martin BG, Sena-Esteves M, et al. Adeno-associated virus(AAV)-mediated gene transfer in respiratory, and submucosal gland cells in human fetal tracheal organ culture[J]. J Pediatr Surg. 2002, 37(7): 1051-1057, discussion 1051-1057.
[6] Benigni A,Tomasoni S,Lutz J, et al.Nonviral and viral gene transfer to the kidney in the context of transplantation[J].Nephron.2000,85(4):307-316.
[7] Kita Y, Li XK, Ohba M,et al.Prolonged cardiac allograft survival in rats systemically injected adenoviml vectors containing CTLA4-Ig -gene [J].Transplantation. 1999,68(6):758-766.
[8] Liu C, Deng S,Yang Z,et al.Local production of CTLA4-Ig by adenoviral-mediated gene transfer to the pancreas induces permanent allograft survival and donor-specific tolerance[J].Transplant Proc.1999,31(1-2):625-626.
[9] Shaked A,Csete ME, Shiraishi M,et al.Retroviral-mediated gene transfer into rat experimental liver transplant[J] Transplantation. 1994,57(1):32-34.
[10] Burdin N, Peronne C, Banchereau J, et al.Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10. J Exp Med[J].1993, 177(2): 295-304.
[11] Ruis P, N assiriM, Gregoriam Set al. Neonataltransp lantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production. T ransplantation[J]. 1996, 61(7): 1198-1201。
[12] Dong, H, Zhu, G, Tamada, K, et al. B7-H1 determines accumulation and deletion ofintrahepatic CDS(+) T lymphocytes. Immunity[J].2004, 20 (3): 327-336.
[13] Burdin N, Peronne C, Banchereau J, et al. Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10. J Exp Med[J].1993, 177(2): 295-304.
[14] Ruis P, N assiriM, Gregoriam S et al. Neonataltransp lantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production. T ransplantation[J]. 1996, 61(7): 1198-1201。
[15] Dong, H, Zhu, G, Tamada, K, et al. B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes. Immunity[J].2004, 20 (3): 327-336.
[16] Seino K, Kayagaki N, Okumura K, et al. Antitumor effect of locally produced CD95 ligand.Nat Med[J].1997, 3(2): 165-70.
[17] Bellgrau D, Gold D, Selawry H, et al. A role for CD95 ligand in preventing graftrejection.Nature[J].1995, 377(65):630-632.
[18] Efrat S, Fejer G, Brownlee M, et al. Prolonged survival of pancreatic islet allografts mediated by adenovirus immunoregulatory transgenes. Proc Natl Acad Sci U S A[J]. 1995, 92(15): 6947-6951。
[19] Ilan Y, Droguett G, Chowdhury NR, et al. Insertion of the adenoviral E3 region into a recombinant viral vector prevents antiviral humoral and cellular immune responses and permits long-term gene expression.Proc Natl Acad Sci U S A[J]. 1997, 94(6): 2587-2592.
[20] Shaked A, Csete ME, Drazan KE, et al.Adenovirus-mediated gene transfer in the transplant setting. Ⅱ. Successful expression of transferred Cdna in syngeneic liver grafts[J]. Transplantation. 1994,57(10): 1508-1511. 21. Turturro F. Recombinant adenovirus-mediated cytotoxic gene therapy of lymphoproliferative disorders: is CAR important for the vector to fide[J]. Gene Ther. 2003, 10(2): 100-104.
[21] Marini FC,3rd, Yu Q, Wickham T, et al. Adenovirus as a gene therapy vector for hematopoietic cells[J]. Cancer Gene Ther.2000,7(6): 816-825.
[22] Heikkila P, Parpala T, Lukkarinen O, et al. Adenovirus-mediated gene transfer into kidney glomeruli using an ex vivo and in vivo kidney perfusion system-first steps towards gene therapy of Alport syndrome[J]. Gene Ther. 1996, 3(1): 21-27.
[1] Giannoukakis N, Thomson A, Robbins P. Gene therapy in transplantation. Gene Ther 1999, 6(9): 1499-511
[2] Koyamada N, Miyatake T, Candinas D, et al. Transient complement inhibition plus T-cell immunosuppression induces long-term survival of mouse-to-rat cardiac xenografts. Transplantation 1998, 65:1210. 31. Soares MP, Lin Y, Anrather J, et al. Expression of heine oxygenase-1 can determine cardiac xenograft survival. Nature Med. 1998, 4: 1073.
[3] Soares MP, Lin Y, Anrather J, et al. Expression of heme oxygenase-1 can determine cardiac xenograft survival. Nature Med. 1998, 4: 1073.
[4] Marshall E. Gene therapy's growing pains. Science 1995, 269(5227): 1050, 1052-5.
[5] Goldspiel BR, Green L, Calis KA, et al. Human gene therapy. Clin Pharm 1993, 12(7): 488-505.
[6] Flotte TR, Afione SA, Conrad C, et al. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with and adeno-associated virus vector. Proc Natl Acad Sci USA 1993, 90(22): 10613-7.
[7] Halbert CL, Alexander IE, Wolgamot GM. Adeno-associated virus vectors transducer primary cells much less efficiently than immortalized cells. J Virol 1995, 69(3): 1473-9
[8] Streck CJ, Zhou J, Ng CY, et al. Longterm recombinant adeno-associated virus-mediated, liver-generated expression of an angiogenesis inhibitor improves survival in mice with disseminated neuroblastoma. J Am Coll Stag 2004, 199(1): 78-86
[9] Zhang X,Shan P, Alam J, et al. Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38alpha mitogen-activated protein kinase pathway during ischemia-reperfusion lung injury. J. Biol. Chem. 2003, 278.
[10] Zhang X, Shan P, Otterbein L E, et al. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J. Biol. Chem. 2003, 278.
[11] Brouard S, Berberat PO, Tobiasch E, et al. Heme oxygenase-1-derived carbon monoxide requires the activation of transcription factor N-F-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis. J. Biol. Chem. 2002, 277.
[12] Daniel S, Arvelo MB, Patel Ⅵ, et al. Ferran, C. A20 protects endothelial cells from TNF-, FAS- and NK-mediated cell death by inhibiting caspase 8 activation. Blood, 2004, 104: 2376.
[13] Berberat P. O, Katori M, Kaczmarek E, et al. Heavy chain ferritin acts as an antiapoptotic gene that protects livers from ischemia reperfusion injury. FASEB J.2003,17:1724.46. Arosio P, Levi S. Ferritin, iron homeostasis, and oxidative damage. Free Radic. Biol. Med. 2002, 33: 457.47. Baranano, D. E, Rao, M, Ferris, C. D, et al. Biliverdin reductase: a major physiologic cytoprotectant [comment]. Proc. Natl. Acad. Sci. USA 2002, 99: 16093.
[14] Akamatsu Y, Haga M, Tyagi S, et al. Heme oxygenase-1-derived carbon monoxideprotects hearts from transplant associate ischemia reperfusion injury. FASEB J. 2004, 18: 771.
[15] Poss KD, Tonegawa S. Heme oxygenase 1 is required for mammalian iron reutilization. Proc. Natl. Acad. Sci. USA, 1997, 94: 10919.
[16] Pae HO, Oh GS, Choi BM, et al. Carbon monoxide produced by heine oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production. J. Immunol. 2004, 172: 4744.
[17] Braudeau C, Bouchet D, Tesson L, et al. Induction of long-term cardiac allograft survival by heme oxygenase-1 gene transfer. Gene Ther. 2004,11: 701.
[18] Song R, Mahidhara R. S, Zhou Z, et al. Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway. J. Immunol. 2004, 172: 1220.
[19] Krijgsman B, Papadakis JA, Ganotakis ES, et al. The effect of peripheral vascular disease on the serum levels of natural anti-oxidants: bilirubin and albumin. Int. Angiol. 2002, 21: 44.
[20] 卢圣栋主编．现代分子生物学实验技术．第二版．北京：协和医科大学出版社，1999
[21] Wang YN, Luk JM, Chung S, et al. In situ transfer rat auxiliary liver transplant. Transplantation 1997, 64(11): 1537-41 29. Ilan Y, Saito H, Thummala NR, et al. Adenovirus-mediated gene therapy of liver disease. Seminars Liver Dis 1999, 19(1): 49-59
[22] Samulsci RJ, Chang LS, Shenk T. Helper-free stocks of recombinant adeno-associated virus: normal integration does not require viral gene expression. J Virol 1989, 63(9): 3822-8
[1] Morris, P.J. Transplantation. In Encyclopedia of Immunology (Delves, P. J. and Roitt, I. M., eds) (2nd edn). Academic Press, 1997, 2411-2415.
[2] Medawar, P. Part played by deoxyribonucleic acid in transplantation immunity. Nature, 1958, 182: 62.
[3] Bellingham R. E., Brent L. and Medawar P. B. Actively acquired tolerance of foreign cells. Nature, 1953, 172: 603-606.
[4] Madsen JC, Superina RA, Wood KJ, et al. Immunological unresponsiveness induced by recipient cells transected with donor M14C genes. Nature, t988, 332(6160): 161-164.
[5] Wong W, Stranford SA, Morris P.1, et al. Retroviral gene transfer of a donor class IMHC gene to recipient bone marrow cells induces tolerance to alloantigen in vivo. Transplant Proc; 1997,29(1-2): Ⅰ 130.
[6] Davies HS, Pollard SG, Calne RY Soluble HLA antigens in the circulation of liver graft recipients. Transplantation, 1989, 47(3): 524-527.
[7] Geissler EK, Korzun WJ, Graeb C. Secreted donor-MHC class Ⅰ antigen prolongs liver allograft survival and inhibits recipient anti-donor catatonic T lymphocyte responses. Transplantation, 1997, 64(5): 782=786.
[8] Zavazava N, Kronke M. Soluble HLA class Ⅰ molecules induce apoptosis in all reactive catatonic T lymphoeytes. Nat Med, 1996, 2(9): 1005-1010. Erraturn ⅲ: Nat Med, 1996, 2(11): 1267.
[9] DeBruyne LA, Li K, Chan SY, et al. Lipid-mediated gene transfer of viral IL-10prolongs vascular zed cardiac allograft survival by inhibiting donor-specific cellular and humeral immune responses. Gene Ther, 1998,5(8): 1079-1087.
[10] Qin L, Ding Y, Bromberg JS. Gene transfer of transforming growth factor-beta lprolongs murine cardiac allograft survival by inhibiting cell-mediated immunity. HumGene Ther, 1996,7(16): 1981-1988.
[11] Kita Y, Li XK, Hayashi S, et al. Prolonged rat cardiac allograft survival using adenoviral vector containing the CTLA419 gene. Transplant Proc, 1998, 30(4): 1079-1080.
[12] Chahine AA, Yu M, McKernan MM, et al. Immunomodulation of pancreatic islet allografts in mice with CTLA41g secreting muscle cells. Transplantation, 1995, 59(9): 1313-1318.
[13] Nagano H, Tilney NL. Chronic allograft failure: the clinical problem. Am J Med Sci, 1997, 313(5): 305-309.
[14] Haug CE, Colvin RB, Delmonieo FL, et al. A phase 1 trial of immunosuppression with anti-ICAM-1 (CD54) mAb in renal allograft recipients. Transplantation, 1993, 55(4): 766-772; discussion 772-773.
[15] Stepkowski SM, Wang ME, Condon TP, et al. Protection against allograftr ejection with intercellular adhesion molecule-Ⅰ anfsense oligodeoxynucleotides. Transplantation, 1998, 66(6): 699-707.
[16] Poston RS, Ertrteh M, Pollard J, et al. Ex vivo gene therapy prevents chronic graft vascular disease in cardiac allograft. J Thorac Cardiovascular Surg, 1998, 116(3): 386-396.
[17] von der Leyen HE, Gibbons GH, Morishita R, et al. Gene therapy, inhibiting neointimal vascular lesion.-in vivo transfer of endothelial cell nitric oxide synthasegene. Proc Natl Acad Sci USA, 1995, 92(4): 1137-1141.
[18] Shears LL 2nd, Kibbe MR, Murdock AD, et al. Efficient inhibition of animal hyperplasia by adenovirus-mediated inducible nitric oxide synthase gene transfer torats and pigs in vivo.J Am Coll Surg ,1998,187(3):295-306.
[19] Fulton GJ, Davies MG, Koch W J, et al. Antisense oligonucleotide toproto-oncogene c-myb inhibits the formation of inhibits hyperplasia in experimental vein grafts. J Vase Surg, 1997,25(3):453-63. Erratum in: J Vase Surg ,1997,26(1):23.
[20] Pitsch RJ, Goodman GR, Minion DJ, et al. Inhibition of smooth muscle cell proliferation and migration in vitro by antisense oligonucleotide to c-myb. J Vase Surg, 1996, 23(5): 783-791.
[21] Castier Y, Chemla E, Nierat J, et al. The activity of c-myb antisense oligonueleotide to prevent intimal hyperplasia is nonspecific. J Cardiovasc Surg(Torino), 1998, 39(1): 1-7. TW
[22] Posselt AM, Barker CF, Tomaszewski JE, et al. Induction of donor-specific unresponsiveness by intrathymic islet transplantation. Science, 1990,249(4974): 1293-1295.
[23] Knechtle S J, Wang J, Jiao S, et al. Induction of specific tolerance by intrathymic injection of recipient muscle cells transected with donor class Ⅰ majorhistocompatibility complex. Transplantation, 1994,57(7): 990-996.
[24] Chia SH, Geller DA, Kibbe MR, et al. Adenovirus-mediated gene transfer to livergrafts an improved method to maximizeinfeetivity. Transplantation, 1998, 66(11): 1545-155Ⅰ.
[25] Nakauchi Hematopoietic stem cells are they CD34 positive or CD34-negative? Nat Med, 1998, 4(9): 1009-1010.
[26] Du Z Ricordi C, podack E, et al. In vitro characterization of hammerhead ribozymes against perforin and fas-ligand RNA. Transplant proc, 1997. 29(4): 2224-2225.
[1] MD Maines, GM Trakshel, and RK Kutty Characterization of two constitutive forms of rat liver microsomal heine oxygenasc. Only one molecular species of the enzyme is inducible J. Biol. Chem. 1986 261: 411-419.
[2] Trakshel GM, Maines MD. Multiplicity of heine oxygenasc isozymes. HO-1 and HO-2 are different molecular species in rat and rabbit. J. Biol. Chem. 1989 264: 1323-1328.
[3] McCoubrey W, Huang T, Maines M. Isolation and characterization of a cDNA from the rat brain thatencodes hemoprotein heine oxygenase-3. Eur J Biochem 1997; 247:725-732.
[4] Wise CD, Drabkin DL. Degradation of haemogiobin and hemin to biliverdin by a new cell-free system obtained from the hemophagous organ of dog placenta. Fed Proc 23: 323.
[5] Llesuy SF, Tomato ML Heine oxygenase and oxidative stress. Evidence of involvement of bilirubin as physiological protector against oxidative damage. Biochim. Biophys. Acta 1994, 1223(1): 9-14.
[6] Poss KD, Tonegawa S. Heine oxygenase 1 is required for mammalian iron reutilization. Proc Nail Acad. Proc Nail Acad Sci.1997, 94(20): 10919-24.
[7] Avihingsanon Y, Ma N, Csizmadia E,et al. Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection. Transplantation, 2002, 73: 1079.
[8] Sikorski EM, Hock T, Agarwal A. The story so far: molecular regulation of the hemeoxygenase-1 gene in renal injury. Am. J. Physiol. Renal Physiol. 2004, 286: F425.
[9] Kimpara T, Takeda A, Watanabe K, et al. Microsatellite polymorphism in the human heine oxygenase-1 gene promoter and its application in association studies with Alzheimer and Parkinson disease. Hum. Genet, 1997,100:145.
[10] Exner M, Minar E, Wagner O,et al. The role of heine oxygcnase-1 promoter polynorphism on human disease. Free Radic. Biol. Med. 2004, 37: 1097.
[11] Baan C, Peeters A, Lcmos F, et al. Fundamental role for HO-1 in the self-protection of renal allografts. Am. J. Transplant,2004,4:811.
[12] Exner M, Bohmig G.A, Schillingcr M,et al. Donor heine oxygenase-1 genotype is associated with renal allograft function. Transplantation 2004, 77: 538.
[13] Daniel S, Arvelo MB, Patel Ⅵ, et al. Ferran, C. A20 protects endothelial cells from TNF-, FAS- and NK-mediated cell death by inhibiting easpase 8 activation. Blood, 2004, 104: 2376.
[14] Lu F, Zander DS,Visner GA. Increased expression of heme oxygenase-1 in human lung transplantation. J. Heart Lung Transplant. 2002, 21: 1120.
[15] Visner GA, Lu F, Zhou H,et al. Graft protective effects of berne oxygenase 1 in mouse tracheal transplant-related obliterative bronchiolitis. Transplantation, 2003, 76: 650.
[16] Deramaudt T B, da Silva, Remy, P, et al. Negative regulation of human hemeoxygenase in microvessel endothelial cells by dexamethasone. Proc. Soc. Exp. Biol. Med. 1999, 222: 185.
[17] Visner G A, Lu F, Zhou H, et al. Rapamycin induces heme oxygenase-1 in human pulmonary vascular cells: implications in the antiproliferative response to rapamycin. Cireulation, 2003, 107: 911.
[18] Li W, Iyer S, Lu L, et al. Attenuation of aortic graft arteriosclerosis by systemic administration ofAUotrap peptide RDP58. Transplant. Int. 2003, 16: 849.
[19] Meier-Kriesche, Schold J. D, Kaplan B. Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies?Am. J. Transplant. 2004, 4: 1289.
[20] Raeusen L C, Solez K, Colvin R. Fibrosis and atrophy in the renal allograft: interim report and new directions. Am. J. Transplant. 2002, 2:203.
[21] Racusen L. C, Halloran P. F, Solez K. Banff 2003 meeting report: new diagnostic insights and standards. Am. J. Transplant 4:1562, 2004.
[22] Joosten S. A, van Kooten C, Sijpkens, Y. W, et al. The pathobiology of chronic allograft nephropathy: immune-mediated damage and accelerated aging. Kidney Int. 2004, 65: 1556.
[23] Kirk A. D. Transplantation: integrating the concepts of innate and acquired immunity with translational trials. Curr. Opin. Immunol. 2004, 16: 535.
[24] Nankivell B. J, Borrows R. J, Fung C. Let al. The natural history of chronic allograft nephropathy. N. Engl. J. Med. 2003, 349: 2326.
[25] Kirk A. D. Transplantation: integrating the concepts of innate and acquired immunity with translational trials. Curr. Opin. Immunol. 2004, 16: 535.
[26] Nankivell B. J, Borrows R. J, Fung C. Let al. The natural history of chronic allograft nephropathy. N. Engl. J. Med. 2003, 349: 2326.
[27] Soares M. P, Lin Y, Sato K, et al. Pathogenesis of and potential therapies for delayed xenograft rejection. Curr. Opin. Organ Transplant, 19994: 80.
[28] Otterbein LE, Soares M P, Yamashita K, et al. Heine oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 2003,24: 449.
[29] Pober JS, Cotran RS. The role of endothelial cells in inflammation. Transplantation, 1990, 50: 537.
[30]. Soares MP, Brouard S, Smith RN, et al. Expression of heme oxygenase-1 by endothelial cells: a protective response to injury in transplantation. Emerging Therapeutic Targets,2000, 4: 11.
[31] Park MT, Choi JA, Kim MJ, et al. Suppression of extracellular signal-related kinase and activation of p38 MAPK are two critical events leading to caspase-8- and mitochondria-mediated cell death in phytosphingosine-treated human cancer cells. J. Biol. Chem. 2003, 278: 50624.
[32] Das DK, Maulik N, Sato M, et al. Reactive oxygen species function as second messenger during ischemic preconditioning of heart. Mol. Cell. Biochem. 1999, 196: 59.
[33] Chalasani G, Li Q, Konieczny B. T, et al. The allograft defines the type of rejection (acute versus chronic) in the face of an established effector immune response. J.Immunol. 2004,172: 7813.
[34] Bach FH, Turman MA, Vercellotti GM.et al. Accommodation: a working paradigm for progressing toward clinical discordant xenografting. Transplant. Proc. 1991, 23: 205.
[35] Bach FH, Ferran C, Hechenleitner P, et al. Accommodation of vascularized xenografls: expression of bprotective genesQ by donor endothelial cells in a host Th2 cytokine environment. Nature Med. 1997, 3: 196.
[36] Hayashi S, Omata Y, Sakamoto H, et al. Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene. Gene, 2004, 336: 241.
[37] Koyamada N, Miyatake T, Candinas D, et al. Transient complement inhibition plus T-cell immunosuppression induces long-term survival of mouse-to-rat cardiac xenografts. Transplantation 1998, 65: 1210.
[38] Soares MP, Lin Y, Anrather J, et al. Expression of heine oxygenase-1 can determine cardiac xenograft survival. Nature Med. 1998, 4: 1073.
[39] Fujita T, Todal K, Karimoval A, et al. Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis. Nature Med. 2001, 7: 598.
[40] Katori M, Buelow R, Ke B,et al. Heme oxygenase-1 overexpression protects rat hearts from cold ischemia/reperfusion injury via an antiapoptotic pathway. Transplantation, 2002, 73: 287.
[41] Tullius SG, Nieminen-Kelha M, Buelow R, et al. Inhibition of ischemia/reperfusion injury and chronic graft deterioration by a single-donor treatment with cobalt-protopor phyrin for the induction of heme oxygenase-1. Transplantation, 2002, 74: 591..
[42] Amersi F, Buelow R, Kato H, et al. Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. J. Clin. Invest. 1999, 104: 1631.
[43] Soares MP, Usheva A, Brouard S, et al. Modulation of endothelial cell apoptosis by heine oxygenase-1-dedved carbon monoxide. Antiox. Redox. Signal. 2002, 4: 321.
[44] Korb, L. C, Ahearn, J. M. Clq binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J. Immunol. 1997,158: 4525.
[45] Zhang X, Shan P, Alam J, et al. Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38alpha mitogen-activated protein kinase pathway during ischemia-reperfusion lung injury. J. Biol. Chem. 2003, 278.
[46] Zhang X, Shah P, Otterbein L E, et al. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J. Biol. Chem. 2003, 278.
[47] Brouard S, Berberat PO, Tobiasch E, et al. Heine oxygenase-1-derived carbon monoxide requires the activation of transcription factor NF-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis. J. Biol. Chem. 2002, 277.
[48] Taille C, El-Benna J, Lanone S Dang,et al. Induction of heme oxygenase-1 inhibits NAD(P)H oxidase activity by down-regulating cytochrome b558 expression via the reduction ofheme availability. J. Biol. Chem. 2004,279:286
[49] Arruda MA, Rossi AG, de Freitas, M. S,et al. Heine inhibits human neutrophil apoptosis: involvement of phosphoinositide 3-kinase, MAPK, and NF-kappaB. J.Immunol. 2004,173:2023.
[50] Ferds C,Jaffrey S, Sawa A, et al. Haem oxygenase-1 prevents cell death by regulating cellular iron. Nature Cell Biol. 1999,1: 152.
[51] Cozzi A, Corsi B, Levi S,et al. Analysis of the biologic functions of H- and L-ferritins in HeLa cells by transfection with siRNAs and cDNAs: evidence for a proliferative role of L-ferritin. Blood,2004,103:2377.
[52] Berberat P. O, Katori M, Kaczmarek E,et al. Heavy chain ferdtin acts as an antiapoptotic gene that protects livers from ischemia reperfusion injury. FASEB J. 2003, 17: 1724.
[53] Arosio P, Levi S. Ferritin, iron homeostasis, and oxidative damage. Free Radic. Biol.Med. 2002, 33:457.
[54] Baranano, D. E, Rao, M, Ferris, C. D, et al. Biliverdin reductase: a major physiologic cytoprotectant [comment]. Proc. Natl.Acad. Sci. USA 2002,99:16093.
[55] Hayashi S,Takamiya R, Yamaguchi T, et al. Induction of Heine oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. Circ. Res. 1999, 85: 663.
[56] Akamatsu Y, Haga M, Tyagi S, et al. Heme oxygenase-1-derived carbon monoxideprotects hearts from transplant associate ischemia reperfusion injury. FASEB J. 2004, 18: 771.
[57] Lucas KA, Pitari GM, Kazerounian S, et al. Guanylyl cyclases and signaling by cyclic GMP. Pharmacol. Rev. 2000, 52: 375.
[58] 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. Immunol. 2001, 166: 4185.
[59] Brune B, Schmidt KU, Ullrich V. Activation of soluble guanylate cyclase by carbon monoxide and inhibition by superoxide anion. Eur. J. Biochem. 1990,192:683.
[60] Otterbein LE, Bach FH, Alam J,et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nature Med. 2000, 6:422.
[61] Soares MP, Lin Y, Anrather J,et al. Expression of heme oxygenase-1 (HO-1) can determine cardiac xenograft survival. Nature Med. 1998,4:1073.
[62] Wada T, Penninger JM. Mitogen-activated protein kinases in apoptosis regulation. Oncogene, 2004, 23: 2838.
[63] Donckier V, Loi P, Closset J, et al. Preconditioning of donors with interleukin-10 reduces hepatic ischemia-reperfusion injury after liver transplantation in pigs.Transplantation,2003, 75:902.
[64] Moore KW, de Waal Malefyt R, Coffman RL,et al. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 2001, 19: 683.
[65] Lee TS, Chau LY. Heme oxygenase-1 mediates the antiinflammatory effect of interleukin-10 in mice. Nature Med. 2002, 8: 240.
[66]. Soares MP. VEGF: is it just an inducer of heme oxygenase-1 expression. Blood, 2004,103:751.
[67] Poss KD, Tonegawa S. Heme oxygenase 1 is required for mammalian iron reutilization.Proc. Natl. Acad. Sci. USA,1997, 94:10919.
[68] Pae HO, Oh GS, Choi BM,et al. Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production.J. Immunol.2004,172:4744.
[69] Braudeau C, Bouchet D, Tesson L,et al. Induction of long-term cardiac allograft survival by heme oxygenase-1 gene transfer. Gene Ther. 2004,11:701.
[70] Song R, Mahidhara R. S, Zhou Z,et al. Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway. J. Immunol. 2004,172:1220.
[71] Araujo JA, Meng L, Tward AD,et al. Systemic rather than local heme oxygenase-1 overexpression improves cardiac allograft outcomes in a new transgenie mouse. J. Immunol. 2003,171:1572.
[72] Bouche D, Chauveau C,Roussel JC, et al. Inhibition of graft arteriosclerosis development in rat aortas following heme oxygenase-1 gene transfer. Transplant. Immunol. 2002, 9: 235.
[73] Otterbein LE; Zuckerbraun BS, Haga M, et al. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nature Med. 2003, 9: 183.
[74] Peyton KJ, Reyna SV, Chapman GB,et al. Heme oxygenase-1-derived carbon monoxide is an autocrine inhibitor of vascular smooth muscle cell growth. Blood, 2002,99:4443.
[75] Krijgsman B, Papadakis JA, Ganotakis ES, et al. The effect of peripheral vascular disease on the serum levels of natural anti-oxidants: bilirubin and albumin. Int. Angiol. 2002, 21: 44.
[2] 郑树森主编．肝脏移植．北京：人民卫生出版社，2001．139
[3] Miyata M, Fisher J, Fuhs M, et al. A simple method for orthotopic liver transplantation in the rat. Transplantation, 1980, 30: 335～338
[4] Kobayashi E, Kamada N, Goto S, et al. Protocol for the techinique of orthotopic liver transplantation in the rot. Microsurgery, 1993, 14: 541～546
[5] Delriviere L, Gibbs P, Kobayashi E, et al. Detailed modified technique for safer harvesting and preparation of liver graft in the rat. Microsurgery, 1996, 17(12): 690～696
[6] Schemmer P, Schoonhoven R, Swenberg JA, et al. Gental in situ liver manipulation during organ harvest decreases survival after rat liver transplantation. Role of Kupffer cells. Transplantation, 1998, 42: 330～331
[7] Tokunaga Y, Ozaki N, Wakashiro S, et al. Effects of perfusion pressure during plushing on the viability of the procured liver using noninvasive fluorometry. Transplantation, 1988, 45: 1031
[8] Marni A, Ferrero ME, Forti D, et al. Advantages of cuff techniques versus standard microsurgical techniques in heterotopic nonauxiliary liver transplantation in rats. Transplant Proc, 1987, 91: 3854～3858
[9] Delrivjete L, Gibbs P, Kobayashi E, et al. Technical details for safer venous and biliary anastomoses for liver transplantation in the rat. Microsurgery, 1998, 19(1): 12～18
[10] 王轩，扬甲梅，严以群，等．大鼠原位肝移植不同术式的探讨．中华器官移植杂志，1998，19(2)：76～78
[11] Kamada N, Calne RY. Orthotopic liver transplantation in the rat: technique technique using cuff for portal vein anastomosis and biliary drinage. Transplantation, 1979, 28: 47～49
[12] Goto M, Takei Y, Kawanno S, et al. Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in rat. Hepatology, 1992, 16: 487
[13] Meyer K, Brown MF, Zibari G, et al. ICAM-1 upregulation in distant tissue after hepatic ischemia/reperfusion: a clue to the mechanism of multiple organ failure. J Pediatr Surg, 1998, 33: 350
[14] 孙君泓，吴孟超，曾琪华．300次大鼠原位肝移植．中华器官移植杂志，1990，11：19～21
[15] 张文海，有井滋村，董雨亭．等．大鼠原位肝移植术并发症的预防．中华器官移植杂志，1995，16：12～14
[1] Kelly VR and Sukhatme VP. Gene transfer in the kidney[J]. Am J Physiol.1999,276(1Pt2):F1-9.
[2] Hart DN, Newton MR, Reece-Smith H, et al. Major histoeompatibility complex antigens in the rat pancreas, isolated pancreatic islets, thyroid, and adrenal [J].Transplantation. 1983,36(4): 431-435.
[3] Hart DN and Fabre JW. Mechanism of induction of passive enhancement. Evidence for an interaction of enhancing antibody with donor interstitial dendritic eells[J]. Transplantation. 1982, 33(3): 319-322.
[4] Karl A. Nath. Heme oxygenase-1: a redoubtable response that limits reperfusion injury in the transplanted adipose live. J. Clin. Invest, 1999, 1485-1486.
[5] Lim FY, Martin BG, Sena-Esteves M, et al. Adeno-associated virus(AAV)-mediated gene transfer in respiratory, and submucosal gland cells in human fetal tracheal organ culture[J]. J Pediatr Surg. 2002, 37(7): 1051-1057, discussion 1051-1057.
[6] Benigni A,Tomasoni S,Lutz J, et al.Nonviral and viral gene transfer to the kidney in the context of transplantation[J].Nephron.2000,85(4):307-316.
[7] Kita Y, Li XK, Ohba M,et al.Prolonged cardiac allograft survival in rats systemically injected adenoviml vectors containing CTLA4-Ig -gene [J].Transplantation. 1999,68(6):758-766.
[8] Liu C, Deng S,Yang Z,et al.Local production of CTLA4-Ig by adenoviral-mediated gene transfer to the pancreas induces permanent allograft survival and donor-specific tolerance[J].Transplant Proc.1999,31(1-2):625-626.
[9] Shaked A,Csete ME, Shiraishi M,et al.Retroviral-mediated gene transfer into rat experimental liver transplant[J] Transplantation. 1994,57(1):32-34.
[10] Burdin N, Peronne C, Banchereau J, et al.Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10. J Exp Med[J].1993, 177(2): 295-304.
[11] Ruis P, N assiriM, Gregoriam Set al. Neonataltransp lantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production. T ransplantation[J]. 1996, 61(7): 1198-1201。
[12] Dong, H, Zhu, G, Tamada, K, et al. B7-H1 determines accumulation and deletion ofintrahepatic CDS(+) T lymphocytes. Immunity[J].2004, 20 (3): 327-336.
[13] Burdin N, Peronne C, Banchereau J, et al. Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10. J Exp Med[J].1993, 177(2): 295-304.
[14] Ruis P, N assiriM, Gregoriam S et al. Neonataltransp lantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production. T ransplantation[J]. 1996, 61(7): 1198-1201。
[15] Dong, H, Zhu, G, Tamada, K, et al. B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes. Immunity[J].2004, 20 (3): 327-336.
[16] Seino K, Kayagaki N, Okumura K, et al. Antitumor effect of locally produced CD95 ligand.Nat Med[J].1997, 3(2): 165-70.
[17] Bellgrau D, Gold D, Selawry H, et al. A role for CD95 ligand in preventing graftrejection.Nature[J].1995, 377(65):630-632.
[18] Efrat S, Fejer G, Brownlee M, et al. Prolonged survival of pancreatic islet allografts mediated by adenovirus immunoregulatory transgenes. Proc Natl Acad Sci U S A[J]. 1995, 92(15): 6947-6951。
[19] Ilan Y, Droguett G, Chowdhury NR, et al. Insertion of the adenoviral E3 region into a recombinant viral vector prevents antiviral humoral and cellular immune responses and permits long-term gene expression.Proc Natl Acad Sci U S A[J]. 1997, 94(6): 2587-2592.
[20] Shaked A, Csete ME, Drazan KE, et al.Adenovirus-mediated gene transfer in the transplant setting. Ⅱ. Successful expression of transferred Cdna in syngeneic liver grafts[J]. Transplantation. 1994,57(10): 1508-1511. 21. Turturro F. Recombinant adenovirus-mediated cytotoxic gene therapy of lymphoproliferative disorders: is CAR important for the vector to fide[J]. Gene Ther. 2003, 10(2): 100-104.
[21] Marini FC,3rd, Yu Q, Wickham T, et al. Adenovirus as a gene therapy vector for hematopoietic cells[J]. Cancer Gene Ther.2000,7(6): 816-825.
[22] Heikkila P, Parpala T, Lukkarinen O, et al. Adenovirus-mediated gene transfer into kidney glomeruli using an ex vivo and in vivo kidney perfusion system-first steps towards gene therapy of Alport syndrome[J]. Gene Ther. 1996, 3(1): 21-27.
[1] Giannoukakis N, Thomson A, Robbins P. Gene therapy in transplantation. Gene Ther 1999, 6(9): 1499-511
[2] Koyamada N, Miyatake T, Candinas D, et al. Transient complement inhibition plus T-cell immunosuppression induces long-term survival of mouse-to-rat cardiac xenografts. Transplantation 1998, 65:1210. 31. Soares MP, Lin Y, Anrather J, et al. Expression of heine oxygenase-1 can determine cardiac xenograft survival. Nature Med. 1998, 4: 1073.
[3] Soares MP, Lin Y, Anrather J, et al. Expression of heme oxygenase-1 can determine cardiac xenograft survival. Nature Med. 1998, 4: 1073.
[4] Marshall E. Gene therapy's growing pains. Science 1995, 269(5227): 1050, 1052-5.
[5] Goldspiel BR, Green L, Calis KA, et al. Human gene therapy. Clin Pharm 1993, 12(7): 488-505.
[6] Flotte TR, Afione SA, Conrad C, et al. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with and adeno-associated virus vector. Proc Natl Acad Sci USA 1993, 90(22): 10613-7.
[7] Halbert CL, Alexander IE, Wolgamot GM. Adeno-associated virus vectors transducer primary cells much less efficiently than immortalized cells. J Virol 1995, 69(3): 1473-9
[8] Streck CJ, Zhou J, Ng CY, et al. Longterm recombinant adeno-associated virus-mediated, liver-generated expression of an angiogenesis inhibitor improves survival in mice with disseminated neuroblastoma. J Am Coll Stag 2004, 199(1): 78-86
[9] Zhang X,Shan P, Alam J, et al. Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38alpha mitogen-activated protein kinase pathway during ischemia-reperfusion lung injury. J. Biol. Chem. 2003, 278.
[10] Zhang X, Shan P, Otterbein L E, et al. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J. Biol. Chem. 2003, 278.
[11] Brouard S, Berberat PO, Tobiasch E, et al. Heme oxygenase-1-derived carbon monoxide requires the activation of transcription factor N-F-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis. J. Biol. Chem. 2002, 277.
[12] Daniel S, Arvelo MB, Patel Ⅵ, et al. Ferran, C. A20 protects endothelial cells from TNF-, FAS- and NK-mediated cell death by inhibiting caspase 8 activation. Blood, 2004, 104: 2376.
[13] Berberat P. O, Katori M, Kaczmarek E, et al. Heavy chain ferritin acts as an antiapoptotic gene that protects livers from ischemia reperfusion injury. FASEB J.2003,17:1724.46. Arosio P, Levi S. Ferritin, iron homeostasis, and oxidative damage. Free Radic. Biol. Med. 2002, 33: 457.47. Baranano, D. E, Rao, M, Ferris, C. D, et al. Biliverdin reductase: a major physiologic cytoprotectant [comment]. Proc. Natl. Acad. Sci. USA 2002, 99: 16093.
[14] Akamatsu Y, Haga M, Tyagi S, et al. Heme oxygenase-1-derived carbon monoxideprotects hearts from transplant associate ischemia reperfusion injury. FASEB J. 2004, 18: 771.
[15] Poss KD, Tonegawa S. Heme oxygenase 1 is required for mammalian iron reutilization. Proc. Natl. Acad. Sci. USA, 1997, 94: 10919.
[16] Pae HO, Oh GS, Choi BM, et al. Carbon monoxide produced by heine oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production. J. Immunol. 2004, 172: 4744.
[17] Braudeau C, Bouchet D, Tesson L, et al. Induction of long-term cardiac allograft survival by heme oxygenase-1 gene transfer. Gene Ther. 2004,11: 701.
[18] Song R, Mahidhara R. S, Zhou Z, et al. Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway. J. Immunol. 2004, 172: 1220.
[19] Krijgsman B, Papadakis JA, Ganotakis ES, et al. The effect of peripheral vascular disease on the serum levels of natural anti-oxidants: bilirubin and albumin. Int. Angiol. 2002, 21: 44.
[20] 卢圣栋主编．现代分子生物学实验技术．第二版．北京：协和医科大学出版社，1999
[21] Wang YN, Luk JM, Chung S, et al. In situ transfer rat auxiliary liver transplant. Transplantation 1997, 64(11): 1537-41 29. Ilan Y, Saito H, Thummala NR, et al. Adenovirus-mediated gene therapy of liver disease. Seminars Liver Dis 1999, 19(1): 49-59
[22] Samulsci RJ, Chang LS, Shenk T. Helper-free stocks of recombinant adeno-associated virus: normal integration does not require viral gene expression. J Virol 1989, 63(9): 3822-8
[1] Morris, P.J. Transplantation. In Encyclopedia of Immunology (Delves, P. J. and Roitt, I. M., eds) (2nd edn). Academic Press, 1997, 2411-2415.
[2] Medawar, P. Part played by deoxyribonucleic acid in transplantation immunity. Nature, 1958, 182: 62.
[3] Bellingham R. E., Brent L. and Medawar P. B. Actively acquired tolerance of foreign cells. Nature, 1953, 172: 603-606.
[4] Madsen JC, Superina RA, Wood KJ, et al. Immunological unresponsiveness induced by recipient cells transected with donor M14C genes. Nature, t988, 332(6160): 161-164.
[5] Wong W, Stranford SA, Morris P.1, et al. Retroviral gene transfer of a donor class IMHC gene to recipient bone marrow cells induces tolerance to alloantigen in vivo. Transplant Proc; 1997,29(1-2): Ⅰ 130.
[6] Davies HS, Pollard SG, Calne RY Soluble HLA antigens in the circulation of liver graft recipients. Transplantation, 1989, 47(3): 524-527.
[7] Geissler EK, Korzun WJ, Graeb C. Secreted donor-MHC class Ⅰ antigen prolongs liver allograft survival and inhibits recipient anti-donor catatonic T lymphocyte responses. Transplantation, 1997, 64(5): 782=786.
[8] Zavazava N, Kronke M. Soluble HLA class Ⅰ molecules induce apoptosis in all reactive catatonic T lymphoeytes. Nat Med, 1996, 2(9): 1005-1010. Erraturn ⅲ: Nat Med, 1996, 2(11): 1267.
[9] DeBruyne LA, Li K, Chan SY, et al. Lipid-mediated gene transfer of viral IL-10prolongs vascular zed cardiac allograft survival by inhibiting donor-specific cellular and humeral immune responses. Gene Ther, 1998,5(8): 1079-1087.
[10] Qin L, Ding Y, Bromberg JS. Gene transfer of transforming growth factor-beta lprolongs murine cardiac allograft survival by inhibiting cell-mediated immunity. HumGene Ther, 1996,7(16): 1981-1988.
[11] Kita Y, Li XK, Hayashi S, et al. Prolonged rat cardiac allograft survival using adenoviral vector containing the CTLA419 gene. Transplant Proc, 1998, 30(4): 1079-1080.
[12] Chahine AA, Yu M, McKernan MM, et al. Immunomodulation of pancreatic islet allografts in mice with CTLA41g secreting muscle cells. Transplantation, 1995, 59(9): 1313-1318.
[13] Nagano H, Tilney NL. Chronic allograft failure: the clinical problem. Am J Med Sci, 1997, 313(5): 305-309.
[14] Haug CE, Colvin RB, Delmonieo FL, et al. A phase 1 trial of immunosuppression with anti-ICAM-1 (CD54) mAb in renal allograft recipients. Transplantation, 1993, 55(4): 766-772; discussion 772-773.
[15] Stepkowski SM, Wang ME, Condon TP, et al. Protection against allograftr ejection with intercellular adhesion molecule-Ⅰ anfsense oligodeoxynucleotides. Transplantation, 1998, 66(6): 699-707.
[16] Poston RS, Ertrteh M, Pollard J, et al. Ex vivo gene therapy prevents chronic graft vascular disease in cardiac allograft. J Thorac Cardiovascular Surg, 1998, 116(3): 386-396.
[17] von der Leyen HE, Gibbons GH, Morishita R, et al. Gene therapy, inhibiting neointimal vascular lesion.-in vivo transfer of endothelial cell nitric oxide synthasegene. Proc Natl Acad Sci USA, 1995, 92(4): 1137-1141.
[18] Shears LL 2nd, Kibbe MR, Murdock AD, et al. Efficient inhibition of animal hyperplasia by adenovirus-mediated inducible nitric oxide synthase gene transfer torats and pigs in vivo.J Am Coll Surg ,1998,187(3):295-306.
[19] Fulton GJ, Davies MG, Koch W J, et al. Antisense oligonucleotide toproto-oncogene c-myb inhibits the formation of inhibits hyperplasia in experimental vein grafts. J Vase Surg, 1997,25(3):453-63. Erratum in: J Vase Surg ,1997,26(1):23.
[20] Pitsch RJ, Goodman GR, Minion DJ, et al. Inhibition of smooth muscle cell proliferation and migration in vitro by antisense oligonucleotide to c-myb. J Vase Surg, 1996, 23(5): 783-791.
[21] Castier Y, Chemla E, Nierat J, et al. The activity of c-myb antisense oligonueleotide to prevent intimal hyperplasia is nonspecific. J Cardiovasc Surg(Torino), 1998, 39(1): 1-7. TW
[22] Posselt AM, Barker CF, Tomaszewski JE, et al. Induction of donor-specific unresponsiveness by intrathymic islet transplantation. Science, 1990,249(4974): 1293-1295.
[23] Knechtle S J, Wang J, Jiao S, et al. Induction of specific tolerance by intrathymic injection of recipient muscle cells transected with donor class Ⅰ majorhistocompatibility complex. Transplantation, 1994,57(7): 990-996.
[24] Chia SH, Geller DA, Kibbe MR, et al. Adenovirus-mediated gene transfer to livergrafts an improved method to maximizeinfeetivity. Transplantation, 1998, 66(11): 1545-155Ⅰ.
[25] Nakauchi Hematopoietic stem cells are they CD34 positive or CD34-negative? Nat Med, 1998, 4(9): 1009-1010.
[26] Du Z Ricordi C, podack E, et al. In vitro characterization of hammerhead ribozymes against perforin and fas-ligand RNA. Transplant proc, 1997. 29(4): 2224-2225.
[1] MD Maines, GM Trakshel, and RK Kutty Characterization of two constitutive forms of rat liver microsomal heine oxygenasc. Only one molecular species of the enzyme is inducible J. Biol. Chem. 1986 261: 411-419.
[2] Trakshel GM, Maines MD. Multiplicity of heine oxygenasc isozymes. HO-1 and HO-2 are different molecular species in rat and rabbit. J. Biol. Chem. 1989 264: 1323-1328.
[3] McCoubrey W, Huang T, Maines M. Isolation and characterization of a cDNA from the rat brain thatencodes hemoprotein heine oxygenase-3. Eur J Biochem 1997; 247:725-732.
[4] Wise CD, Drabkin DL. Degradation of haemogiobin and hemin to biliverdin by a new cell-free system obtained from the hemophagous organ of dog placenta. Fed Proc 23: 323.
[5] Llesuy SF, Tomato ML Heine oxygenase and oxidative stress. Evidence of involvement of bilirubin as physiological protector against oxidative damage. Biochim. Biophys. Acta 1994, 1223(1): 9-14.
[6] Poss KD, Tonegawa S. Heine oxygenase 1 is required for mammalian iron reutilization. Proc Nail Acad. Proc Nail Acad Sci.1997, 94(20): 10919-24.
[7] Avihingsanon Y, Ma N, Csizmadia E,et al. Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection. Transplantation, 2002, 73: 1079.
[8] Sikorski EM, Hock T, Agarwal A. The story so far: molecular regulation of the hemeoxygenase-1 gene in renal injury. Am. J. Physiol. Renal Physiol. 2004, 286: F425.
[9] Kimpara T, Takeda A, Watanabe K, et al. Microsatellite polymorphism in the human heine oxygenase-1 gene promoter and its application in association studies with Alzheimer and Parkinson disease. Hum. Genet, 1997,100:145.
[10] Exner M, Minar E, Wagner O,et al. The role of heine oxygcnase-1 promoter polynorphism on human disease. Free Radic. Biol. Med. 2004, 37: 1097.
[11] Baan C, Peeters A, Lcmos F, et al. Fundamental role for HO-1 in the self-protection of renal allografts. Am. J. Transplant,2004,4:811.
[12] Exner M, Bohmig G.A, Schillingcr M,et al. Donor heine oxygenase-1 genotype is associated with renal allograft function. Transplantation 2004, 77: 538.
[13] Daniel S, Arvelo MB, Patel Ⅵ, et al. Ferran, C. A20 protects endothelial cells from TNF-, FAS- and NK-mediated cell death by inhibiting easpase 8 activation. Blood, 2004, 104: 2376.
[14] Lu F, Zander DS,Visner GA. Increased expression of heme oxygenase-1 in human lung transplantation. J. Heart Lung Transplant. 2002, 21: 1120.
[15] Visner GA, Lu F, Zhou H,et al. Graft protective effects of berne oxygenase 1 in mouse tracheal transplant-related obliterative bronchiolitis. Transplantation, 2003, 76: 650.
[16] Deramaudt T B, da Silva, Remy, P, et al. Negative regulation of human hemeoxygenase in microvessel endothelial cells by dexamethasone. Proc. Soc. Exp. Biol. Med. 1999, 222: 185.
[17] Visner G A, Lu F, Zhou H, et al. Rapamycin induces heme oxygenase-1 in human pulmonary vascular cells: implications in the antiproliferative response to rapamycin. Cireulation, 2003, 107: 911.
[18] Li W, Iyer S, Lu L, et al. Attenuation of aortic graft arteriosclerosis by systemic administration ofAUotrap peptide RDP58. Transplant. Int. 2003, 16: 849.
[19] Meier-Kriesche, Schold J. D, Kaplan B. Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies?Am. J. Transplant. 2004, 4: 1289.
[20] Raeusen L C, Solez K, Colvin R. Fibrosis and atrophy in the renal allograft: interim report and new directions. Am. J. Transplant. 2002, 2:203.
[21] Racusen L. C, Halloran P. F, Solez K. Banff 2003 meeting report: new diagnostic insights and standards. Am. J. Transplant 4:1562, 2004.
[22] Joosten S. A, van Kooten C, Sijpkens, Y. W, et al. The pathobiology of chronic allograft nephropathy: immune-mediated damage and accelerated aging. Kidney Int. 2004, 65: 1556.
[23] Kirk A. D. Transplantation: integrating the concepts of innate and acquired immunity with translational trials. Curr. Opin. Immunol. 2004, 16: 535.
[24] Nankivell B. J, Borrows R. J, Fung C. Let al. The natural history of chronic allograft nephropathy. N. Engl. J. Med. 2003, 349: 2326.
[25] Kirk A. D. Transplantation: integrating the concepts of innate and acquired immunity with translational trials. Curr. Opin. Immunol. 2004, 16: 535.
[26] Nankivell B. J, Borrows R. J, Fung C. Let al. The natural history of chronic allograft nephropathy. N. Engl. J. Med. 2003, 349: 2326.
[27] Soares M. P, Lin Y, Sato K, et al. Pathogenesis of and potential therapies for delayed xenograft rejection. Curr. Opin. Organ Transplant, 19994: 80.
[28] Otterbein LE, Soares M P, Yamashita K, et al. Heine oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 2003,24: 449.
[29] Pober JS, Cotran RS. The role of endothelial cells in inflammation. Transplantation, 1990, 50: 537.
[30]. Soares MP, Brouard S, Smith RN, et al. Expression of heme oxygenase-1 by endothelial cells: a protective response to injury in transplantation. Emerging Therapeutic Targets,2000, 4: 11.
[31] Park MT, Choi JA, Kim MJ, et al. Suppression of extracellular signal-related kinase and activation of p38 MAPK are two critical events leading to caspase-8- and mitochondria-mediated cell death in phytosphingosine-treated human cancer cells. J. Biol. Chem. 2003, 278: 50624.
[32] Das DK, Maulik N, Sato M, et al. Reactive oxygen species function as second messenger during ischemic preconditioning of heart. Mol. Cell. Biochem. 1999, 196: 59.
[33] Chalasani G, Li Q, Konieczny B. T, et al. The allograft defines the type of rejection (acute versus chronic) in the face of an established effector immune response. J.Immunol. 2004,172: 7813.
[34] Bach FH, Turman MA, Vercellotti GM.et al. Accommodation: a working paradigm for progressing toward clinical discordant xenografting. Transplant. Proc. 1991, 23: 205.
[35] Bach FH, Ferran C, Hechenleitner P, et al. Accommodation of vascularized xenografls: expression of bprotective genesQ by donor endothelial cells in a host Th2 cytokine environment. Nature Med. 1997, 3: 196.
[36] Hayashi S, Omata Y, Sakamoto H, et al. Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene. Gene, 2004, 336: 241.
[37] Koyamada N, Miyatake T, Candinas D, et al. Transient complement inhibition plus T-cell immunosuppression induces long-term survival of mouse-to-rat cardiac xenografts. Transplantation 1998, 65: 1210.
[38] Soares MP, Lin Y, Anrather J, et al. Expression of heine oxygenase-1 can determine cardiac xenograft survival. Nature Med. 1998, 4: 1073.
[39] Fujita T, Todal K, Karimoval A, et al. Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis. Nature Med. 2001, 7: 598.
[40] Katori M, Buelow R, Ke B,et al. Heme oxygenase-1 overexpression protects rat hearts from cold ischemia/reperfusion injury via an antiapoptotic pathway. Transplantation, 2002, 73: 287.
[41] Tullius SG, Nieminen-Kelha M, Buelow R, et al. Inhibition of ischemia/reperfusion injury and chronic graft deterioration by a single-donor treatment with cobalt-protopor phyrin for the induction of heme oxygenase-1. Transplantation, 2002, 74: 591..
[42] Amersi F, Buelow R, Kato H, et al. Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. J. Clin. Invest. 1999, 104: 1631.
[43] Soares MP, Usheva A, Brouard S, et al. Modulation of endothelial cell apoptosis by heine oxygenase-1-dedved carbon monoxide. Antiox. Redox. Signal. 2002, 4: 321.
[44] Korb, L. C, Ahearn, J. M. Clq binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J. Immunol. 1997,158: 4525.
[45] Zhang X, Shan P, Alam J, et al. Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38alpha mitogen-activated protein kinase pathway during ischemia-reperfusion lung injury. J. Biol. Chem. 2003, 278.
[46] Zhang X, Shah P, Otterbein L E, et al. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J. Biol. Chem. 2003, 278.
[47] Brouard S, Berberat PO, Tobiasch E, et al. Heine oxygenase-1-derived carbon monoxide requires the activation of transcription factor NF-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis. J. Biol. Chem. 2002, 277.
[48] Taille C, El-Benna J, Lanone S Dang,et al. Induction of heme oxygenase-1 inhibits NAD(P)H oxidase activity by down-regulating cytochrome b558 expression via the reduction ofheme availability. J. Biol. Chem. 2004,279:286
[49] Arruda MA, Rossi AG, de Freitas, M. S,et al. Heine inhibits human neutrophil apoptosis: involvement of phosphoinositide 3-kinase, MAPK, and NF-kappaB. J.Immunol. 2004,173:2023.
[50] Ferds C,Jaffrey S, Sawa A, et al. Haem oxygenase-1 prevents cell death by regulating cellular iron. Nature Cell Biol. 1999,1: 152.
[51] Cozzi A, Corsi B, Levi S,et al. Analysis of the biologic functions of H- and L-ferritins in HeLa cells by transfection with siRNAs and cDNAs: evidence for a proliferative role of L-ferritin. Blood,2004,103:2377.
[52] Berberat P. O, Katori M, Kaczmarek E,et al. Heavy chain ferdtin acts as an antiapoptotic gene that protects livers from ischemia reperfusion injury. FASEB J. 2003, 17: 1724.
[53] Arosio P, Levi S. Ferritin, iron homeostasis, and oxidative damage. Free Radic. Biol.Med. 2002, 33:457.
[54] Baranano, D. E, Rao, M, Ferris, C. D, et al. Biliverdin reductase: a major physiologic cytoprotectant [comment]. Proc. Natl.Acad. Sci. USA 2002,99:16093.
[55] Hayashi S,Takamiya R, Yamaguchi T, et al. Induction of Heine oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. Circ. Res. 1999, 85: 663.
[56] Akamatsu Y, Haga M, Tyagi S, et al. Heme oxygenase-1-derived carbon monoxideprotects hearts from transplant associate ischemia reperfusion injury. FASEB J. 2004, 18: 771.
[57] Lucas KA, Pitari GM, Kazerounian S, et al. Guanylyl cyclases and signaling by cyclic GMP. Pharmacol. Rev. 2000, 52: 375.
[58] 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. Immunol. 2001, 166: 4185.
[59] Brune B, Schmidt KU, Ullrich V. Activation of soluble guanylate cyclase by carbon monoxide and inhibition by superoxide anion. Eur. J. Biochem. 1990,192:683.
[60] Otterbein LE, Bach FH, Alam J,et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nature Med. 2000, 6:422.
[61] Soares MP, Lin Y, Anrather J,et al. Expression of heme oxygenase-1 (HO-1) can determine cardiac xenograft survival. Nature Med. 1998,4:1073.
[62] Wada T, Penninger JM. Mitogen-activated protein kinases in apoptosis regulation. Oncogene, 2004, 23: 2838.
[63] Donckier V, Loi P, Closset J, et al. Preconditioning of donors with interleukin-10 reduces hepatic ischemia-reperfusion injury after liver transplantation in pigs.Transplantation,2003, 75:902.
[64] Moore KW, de Waal Malefyt R, Coffman RL,et al. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 2001, 19: 683.
[65] Lee TS, Chau LY. Heme oxygenase-1 mediates the antiinflammatory effect of interleukin-10 in mice. Nature Med. 2002, 8: 240.
[66]. Soares MP. VEGF: is it just an inducer of heme oxygenase-1 expression. Blood, 2004,103:751.
[67] Poss KD, Tonegawa S. Heme oxygenase 1 is required for mammalian iron reutilization.Proc. Natl. Acad. Sci. USA,1997, 94:10919.
[68] Pae HO, Oh GS, Choi BM,et al. Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production.J. Immunol.2004,172:4744.
[69] Braudeau C, Bouchet D, Tesson L,et al. Induction of long-term cardiac allograft survival by heme oxygenase-1 gene transfer. Gene Ther. 2004,11:701.
[70] Song R, Mahidhara R. S, Zhou Z,et al. Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway. J. Immunol. 2004,172:1220.
[71] Araujo JA, Meng L, Tward AD,et al. Systemic rather than local heme oxygenase-1 overexpression improves cardiac allograft outcomes in a new transgenie mouse. J. Immunol. 2003,171:1572.
[72] Bouche D, Chauveau C,Roussel JC, et al. Inhibition of graft arteriosclerosis development in rat aortas following heme oxygenase-1 gene transfer. Transplant. Immunol. 2002, 9: 235.
[73] Otterbein LE; Zuckerbraun BS, Haga M, et al. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nature Med. 2003, 9: 183.
[74] Peyton KJ, Reyna SV, Chapman GB,et al. Heme oxygenase-1-derived carbon monoxide is an autocrine inhibitor of vascular smooth muscle cell growth. Blood, 2002,99:4443.
[75] Krijgsman B, Papadakis JA, Ganotakis ES, et al. The effect of peripheral vascular disease on the serum levels of natural anti-oxidants: bilirubin and albumin. Int. Angiol. 2002, 21: 44.