切换至 "中华医学电子期刊资源库"
高级检索
中华移植杂志(电子版)

中华移植杂志(电子版) ›› 2017, Vol. 11 ›› Issue (01) : 59 -64. doi: 10.3877/cma.j.issn.1674-3903.2017.01.014

所属专题： 总编推荐； 文献；

综述

肺移植后闭塞性细支气管炎动物模型
徐凯英1, 王思桦1, 王建军1,†()   
  1. 1. 430022　武汉，华中科技大学同济医学院附属协和医院胸外科
  • 收稿日期:2016-11-21 出版日期:2017-02-25
  • 通信作者: 王建军
  • 基金资助:
    国家自然科学基金青年基金项目(81401323)

A review for animal models of obliterative bronchiolitis after lung transplantation

Kaiying Xu1, Sihua Wang1, Jianjun Wang1,†()   

  1. 1. Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • Received:2016-11-21 Published:2017-02-25
  • Corresponding author: Jianjun Wang
  • About author:
    Corresponding author: Wang Jianjun, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

徐凯英, 王思桦, 王建军. 肺移植后闭塞性细支气管炎动物模型[J]. 中华移植杂志(电子版), 2017, 11(01): 59-64.

Kaiying Xu, Sihua Wang, Jianjun Wang. A review for animal models of obliterative bronchiolitis after lung transplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2017, 11(01): 59-64.

肺移植已经成为终末期良性肺部疾病的重要治疗方法。随着手术技术、围手术期管理及免疫抑制治疗的发展，肺移植后早期生存率明显提高，但长期生存率却无显著改善。闭塞性细支气管炎(OB)是影响肺移植后长期生存的主要因素。基于动物模型的研究对于我们探索OB发生的病理机制以及研发新的防治措施都是必不可少的。目前，已经建立了许多用于OB研究的动物模型。本文对目前用于OB研究的各种动物模型的优缺点展开综述，期望帮助研究人员选择合适的动物模型。

关键词: 肺移植, 动物模型, 闭塞性细支气管炎, 慢性排斥反应

Lung transplantation has become an important therapy for patients with end-stage benign lung disease. With the progress of surgical technique, perioperative mananment and immunosuppressive therapy, surival rate in early stage after transplant have significantly improved, while long-term surival rate has not changed much. Obliterative bronchiolitis (OB) is the major limitation to long-term surival after lung transplatation. Ivestigation basing on animal models is indispensable to understand the underlying pathological mechanisms and to develop novel preventive and therapetic stragies for OB. So far, many animal models have been developed to study OB. This article reviews the strengths and drawbacks of those animal models, hoping to help researchers in chooseing the appropriate model for their intrended research.

Key words: Lung transplantation, Animal model, Obliterative bronchiolitis, Chronic rejection
1
Hardy JD,Webb WR,Dalton ML Jr, et al. Lung homotransplantation in man[J]. JAMA, 1963, 186: 1065-1074.
2
Yusen RD,Edwards LB,Dipchand AI, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third adult lung and heart-lung transplant report-2016; Focus theme: primary diagnostic indications for transplant[J]. J Heart Lung Transplant, 2016, 35(10): 1170-1184.
3
Sato M,Keshavjee S. Bronchiolitis obliterans syndrome: alloimmune-dependent and -independent injury with aberrant tissue remodeling[J]. Semin Thorac Cardiovasc Surg, 2008, 20(2): 173-182.
4
Hertz MI,Jessurun J,King MB, et al. Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways[J]. Am J Pathol, 1993, 142(6): 1945-1951.
5
Richards DM,Dalheimer SL,Hertz MI, et al. Trachea allograft classⅠmolecules directly activate and retain CD8＋ T cells that cause obliterative airways disease[J]. J Immunol, 2003, 171(12): 6919-6928.
6
Ramirez AM,Shen Z,Ritzenthaler JD, et al. Myofibroblast transdifferentiation in obliterative bronchiolitis: TGF-β signaling through Smad3-dependent and -independent pathways[J]. Am J Transplant, 2006, 6(9): 2080-2088.
7
Gomperts BN,Belperio JA,Rao PN, et al. Circulating progenitor epithelial cells traffic via CXCR4/CXCL12 in response to airway injury[J]. J Immunol, 2006, 176(3): 1916-1927.
8
Mckane BW,Fernandez F,Narayanan K, et al. Pirfenidone inhibits obliterative airway disease in a murine heterotopic tracheal transplant model[J]. Transplantation, 2004, 77(5): 664-669.
9
King MB,Jessurun J,Savik SK, et al. Cyclosporine reduces development of obliterative bronchiolitis in a murine heterotopic airway model[J]. Transplantation, 1997, 63(4): 528-532.
10
Fahrni JA,Berry GJ,Morris RE, et al. Rapamycin inhibits development of obliterative airway disease in a murine heterotopic airway transplant model[J]. Transplantation, 1997, 63(4): 533-537.
11
Belperio JA,Keane MP,Burdick MD, et al. Role of CXCR2/CXCR2 ligands in vascular remodeling during bronchiolitis obliterans syndrome[J]. J Clin Invest, 2005, 115(5): 1150-1162.
12
Richards DM,Dalheimer SL,Ehst BD, et al. Indirect minor histocompatibility antigen presentation by allograft recipient cells in the draining lymph node leads to the activation and clonal expansion of CD4＋ T cells that cause obliterative airways disease[J]. J Immunol, 2004, 172(6): 3469-3479.
13
Huang XH,Reichenspurner H,Shorthouse R, et al. Heterotopic tracheal allograft transplantation: a new model to study the molecular events causing obliterative airway disease (OAD) in rats[J]. J Heart Lung Transplant, 1995, 14(suppl): 49.
14
Boehler A,Chamberlain D,Kesten S, et al. Lymphocytic airway infiltration as a precursor to fibrous obliteration in a rat model of bronchiolitis obliterans[J]. Transplantation, 1997, 64(2): 311-317.
15
Ikonen TS,Brazelton TR,Berry GJ, et al. Epithelial re-growth is associated with inhibition of obliterative airway disease in orthotopic tracheal allografts in non-immunosuppressed rats[J]. Transplantation, 2000, 70(6): 857-863.
16
Dutly AE,Andrade CF,Verkaik R, et al. A novel model for post-transplant obliterative airway disease reveals angiogenesis from the pulmonary circulation[J]. Am J Transplant, 2005, 5(2): 248-254.
17
Sato M,Liu M,Anraku M, et al. Allograft airway fibrosis in the pulmonary milieu: a disorder of tissue remodeling[J]. Am J Transplant, 2008, 8(3): 517-528.
18
Nakanishi R,Shirakusa T,Hanagiri T. Early histopathologic features of tracheal allotransplant rejection: a study in nonimmunosuppressed dogs[J]. Transplant Proc, 1994, 26(6): 3715-3718.
19
Hertz MI,Jessurun J,King MB, et al. Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways[J]. Am J Pathol, 1993, 142(6): 1945-1951.
20
Xavier-Elsas P,Santos-Maximiano E,Queto T, et al. Ectopic lung transplantation induces the accumulation of eosinophil progenitors in the recipients′ lungs through an allergen- and interleukin-5-dependent mechanism[J]. Clin Exp Allergy, 2007, 37(1): 29-38.
21
Ikonen T,Uusitalo M,Taskinen E, et al. Small airway obliteration in a new swine heterotopic lung and bronchial allograft model[J]. J Heart Lung Transplant, 1998, 17(10): 945-953.
22
Salminen US,Ikonen T,Uusitalo M, et al. Obliterative lesions in small airways in an immunosuppressed porcine heterotopic bronchial allograft model[J]. Transpl Int, 1998, 11(Suppl 1): S515-S518.
23
Uusitalo MH,Salminen US,Ikonen TS, et al. Alloimmune injury preceding airway obliteration in porcine heterotopic lung implants: a histologic and immunohistologic study[J]. Transplantation, 1999, 68(7): 970-975.
24
Salminen US,Alho H,Taskinen E, et al. Effects of rapamycin analogue SDZ RAD on obliterative lesions in a porcine heterotopic bronchial allograft model[J]. Transplant Proc, 1998, 30(5): 2204-2205.
25
Hausen B,Berry GJ,Dagum P, et al. The histology of subcutaneously implanted donor bronchial rings correlates with rejection scores of lung allografts in a primate lung transplant model[J]. J Heart Lung Transplant, 1999, 18(7): 714-724.
26
Genden EM,Boros P,Liu J, et al. Orthotopic tracheal transplantation in the murine model[J]. Transplantation, 2002, 73(9): 1420-1425.
27
Genden EM,Iskander A,Bromberg JS, et al. The kinetics and pattern of tracheal allograft re-epithelialization[J]. Am J Respir Cell Mol Biol, 2003, 28(6): 673-681.
28
Murakawa T,Kerklo MM,Zamora MR, et al. Simultaneous LFA-1 and CD40 ligand antagonism prevents airway remodeling in orthotopic airway transplantation: implications for the role of respiratory epithelium as a modulator of fibrosis[J]. J Immunol, 2005, 174(7): 3869-3879.
29
Cleven HA,Genden EM,Moran TM. Reepithelialized orthotopic tracheal allografts expand memory cytotoxic T lymphocytes but show no evidence of chronic rejection[J]. Transplantation, 2005, 79(8): 861-868.
30
Kuo E,Bharat A,Goers T, et al. Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation[J]. Ann Thorac Surg, 2006, 82(3): 1043-1050.
31
Kuo E,Bharat A,Shih J, et al. Role of airway epithelial injury in murine orthotopic tracheal allograft rejection[J]. Ann Thorac Surg, 2006, 82(4): 1226-1233.
32
Babu AN,Murakawa T,Thurman JM, et al. Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis[J]. J Clin Invest, 2007, 117(12): 3774-3785.
33
Genden EM,Iskander AJ,Bromberg JS, et al. Orthotopic tracheal allografts undergo reepithelialization with recipient-derived epithelium[J]. Arch Otolaryngol Head Neck Surg, 2003, 129(1): 118-123.
34
Ito Y,Takahashi T,Suzuki K, et al. Inhibition of epithelial replacement by nonspecific immunosuppressants accelerates rat orthotopic tracheal allograft rejection[J]. Transplant Proc, 2002, 34(5): 1441-1442.
35
Ito Y,Suzuki H,Hattori Y, et al. Complete replacement of tracheal epithelia by the host promotes spontaneous acceptance of orthotopic tracheal allografts in rats[J]. Transplant Proc, 2004, 36(8): 2406-2412.
36
Nakanishi R,Hashimoto M,Yasumoto K. Improved airway healing using basic fibroblast growth factor in a canine tracheal autotransplantation model[J]. Ann Surg, 1998, 227(3): 446-454.
37
Behrend M,von Wasielewski R,Klempnauer J. Failure of airway healing in an ovine autotransplantation model that includes basic fibroblast growth factor[J]. J Thorac Cardiovasc Surg, 2002, 124(2): 231-240.
38
Behrend M,Kluge E. The fate of homograft tracheal transplants in sheep[J]. World J Surg, 2008, 32(8): 1669-1675.
39
Asimacopoulos PJ,Molokhia FA,Pegg CA, et al. Lung transplantation in the rat[J]. Transplant Proc, 1971, 3(1): 583-585.
40
Mizuta T,Kawaguchi A,Nakahara K, et al. Simplified rat lung transplantation using a cuff technique[J]. J Thorac Cardiovasc Surg, 1989, 97(4): 578-581.
41
Kamada N,Calne RY. Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage[J]. Transplantation, 1979, 28(1): 47-50.
42
Mizobuchi T,Sekine Y,Yasufuku K, et al. Comparison of surgical procedures for vascular and airway anastomoses that utilize a modified non-suture external cuff technique for experimental lung transplantation in rats[J]. J Heart Lung Transplant, 2004, 23(7): 889-893.
43
Zhai W,Ge J,Inci I, et al. Simplified rat lung transplantation by using a modified cuff technique[J]. J Invest Surg, 2008, 21(1): 33-37.
44
Goto T,Kohno M,Anraku M, et al. Simplified rat lung transplantation using a new cuff technique[J]. Ann Thorac Surg, 2012, 93(6): 2078-2080.
45
Zhang QC,Wang DJ,Yin N, et al. The orthotopic left lung transplantation in rats: a valuable experimental model without using cuff technique[J]. Transpl Int, 2008, 21(11): 1090-1097.
46
Prop J,Wildevuur CR,Nieuwenhuis P. Lung allograft rejection in the rat. Ⅲ. Corresponding morphological rejection phases in various rat strain combinations[J]. Transplantation, 1985, 40(2): 132-136.
47
Prop J,Nieuwenhuis P,Wildevuur CR. Lung allograft rejection in the rat. Ⅰ. Accelerated rejection caused by graft lymphocytes[J]. Transplantation, 1985, 40(1): 25-30.
48
Prop J,Wildevuur CR,Nieuwenhuis P. Lung allograft rejection in the rat. Ⅱ. Specific immunological properties of lung grafts[J]. Transplantation, 1985, 40(2): 126-131.
49
Prop J,Jansen HM,Wildevuur CR, et al. Lung allograft rejection in the rat. Ⅴ. Inhaled stimuli aggravate the rejection response[J]. Am Rev Respir Dis, 1985, 132(1): 168-172.
50
Romaniuk A,Prop J,Petersen AH, et al. Expression of class Ⅱ major histocompatibility complex antigens by bronchial epithelium in rat lung allografts[J]. Transplantation, 1987, 44(2): 209-214.
51
Matsumura Y,Marchevsky A,Zuo XJ, et al. Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation[J]. Transplantation, 1995, 59(11): 1509-1517.
52
Uyama T,Winter JB,Groen G, et al. Late airway changes caused by chronic rejection in rat lung allografts[J]. Transplantation, 1992, 54(5): 809-812.
53
Hirt SW,You XM,Möller F, et al. Development of obliterative bronchiolitis after allogeneic rat lung transplantation: implication of acute rejection and the time point of treatment[J]. J Heart Lung Transplant, 1999, 18(6): 542-548.
54
Jungraithmayr W,Vogt P,Inci I, et al. A model of chronic lung allograft rejection in the rat[J]. Eur Respir J, 2010, 35(6): 1354-1363.
55
Winter JB,Gouw AS,Groen M, et al. Respiratory viral infections aggravate airway damage caused by chronic rejection in rat lung allografts[J]. Transplantation, 1994, 57(3): 418-422.
56
Yagyu K,van Breda Vriesman PJ,Duijvestijn AM, et al. Reactivation of cytomegalovirus with acute rejection and cytomegalovirus infection with obliterative bronchiolitis in rat lung allografts[J]. Transplant Proc, 1993, 25(1 Pt 2): 1152-1154.
57
Okazaki M,Krupnick AS,Kornfeld CG, et al. A mouse model of orthotopic vascularized aerated lung transplantation[J]. Am J Transplant, 2007, 7(6): 1672-1679.
58
Jungraithmayr WM,Korom S,Hillinger S, et al. A mouse model of orthotopic, single-lung transplantation[J]. J Thorac Cardiovasc Surg, 2009, 137(2): 486-491.
59
Li W,Sugimoto S,Lai J, et al. Orthotopic vascularized right lung transplantation in the mouse[J]. J Thorac Cardiovasc Surg, 2010, 139(6): 1637-1643.
60
Fan L,Benson HL,Vittal R, et al. Neutralizing IL-17 prevents obliterative bronchiolitis in murine orthotopic lung transplantation[J]. Am J Transplant, 2011, 11(5): 911-922.
61
Zheng Z,Wang J,Huang X, et al. Improvements of the surgical technique on the established mouse model of orthotopic single lung transplantation[J]. PLoS One, 2013, 8(11): e81000.
62
乔新伟,江科,李劲松, 等. 改良三套管法建立小鼠左肺原位移植模型[J]. 华中科技大学学报(医学版), 2014(2): 158-161.
63
Gelman AE,Okazaki M,Lai J, et al. CD4＋ T lymphocytes are not necessary for the acute rejection of vascularized mouse lung transplants[J]. J Immunol, 2008, 180(7): 4754-4762.
64
Draenert A,Marquardt K,Inci I, et al. Ischaemia-reperfusion injury in orthotopic mouse lung transplants - a scanning electron microscopy study[J]. Int J Exp Pathol, 2011, 92(1): 18-25.
65
Jungraithmayr W,De Meester I,Matheeussen V, et al. Inhibition of CD26/DPP Ⅳ attenuates ischemia/reperfusion injury in orthotopic mouse lung transplants: the pivotal role of vasoactive intestinal peptide[J]. Peptides, 2010, 31(4): 585-591.
66
De Vleeschauwer S,Jungraithmayr W,Wauters S, et al. Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks[J]. PLoS One, 2012, 7(1): e29802.
67
al-Dossari GA,Kshettry VR,Jessurun J, et al. Experimental large-animal model of obliterative bronchiolitis after lung transplantation[J]. Ann Thorac Surg, 1994, 58(1): 34-39.
68
Schmid RA,Kwong K,Boasquevisque CH, et al. A chronic large animal model of lung allograft rejection[J]. Transplant Proc, 1997, 29(1-2): 1521.
69
Allan JS,Wain JC,Schwarze ML, et al. Modeling chronic lung allograft rejection in miniature swine[J]. Transplantation, 2002, 73(3): 447-453.
70
Sahara H,Weiss MJ,Ng CY, et al. Thymectomy does not abrogate long-term acceptance of MHC classⅠ-disparate lung allografts in miniature Swine[J]. Transplant Proc, 2006, 38(10): 3253-3255.
71
Shoji T,Sahara H,Muniappan A, et al. An MHC class Ⅱ disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine[J]. Transplant Proc, 2006, 38(10): 3268-3270.
72
Warnecke G,Avsar M,Steinkamp T, et al. Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine[J]. Eur J Cardiothorac Surg, 2005, 28(3): 454-460.
[1] 黄钰清, 武杜杜, 潘菲, 王俊康, 钟兆明, 黎檀实, 吕发勤. 掌上超声在枪弹伤致髂动脉破裂大出血建模中的应用研究[J]. 中华医学超声杂志（电子版）, 2022, 19(10): 1112-1117.
[2] 轩晨昊, 许红阳. 降钙素原对双肺移植患者术后痰培养阳性的预测价值研究[J]. 中华危重症医学杂志(电子版), 2023, 16(03): 211-214.
[3] 李传举, 刘林月, 王美, 李昕, 韩祥辉, 贾海永. 乙型肝炎病毒感染模型研究进展[J]. 中华实验和临床感染病杂志(电子版), 2022, 16(06): 361-365.
[4] 中华医学会器官移植学分会肺移植学组, 国家肺移植质控中心. 新型冠状病毒感染肺移植受者选择中国专家建议[J]. 中华移植杂志(电子版), 2023, 17(01): 13-16.
[5] 惠姣洁, 梁锋鸣, 王逸峰, 王大鹏, 陈静瑜, 许红阳. 肺移植术后体外膜肺氧合流量不足处理经验[J]. 中华移植杂志(电子版), 2022, 16(04): 238-240.
[6] 吴婷, 孙燕燕, 郑媛媛, 韩威力. 支气管扩张合并强直性脊柱炎单肺移植一例[J]. 中华移植杂志(电子版), 2022, 16(04): 235-237.
[7] 王桂龙, 顾正峰, 吴金波, 胡春晓, 秦钟, 张昕, 陈静瑜. 双肺移植手术室内拔管二例[J]. 中华肺部疾病杂志(电子版), 2023, 16(01): 138-140.
[8] 邵世锋, 伍正彬, 段朝霞, 张良潮, 王耀丽, 李琦, 王建民. 山羊高原重度原发性肺冲击伤模型的建立[J]. 中华肺部疾病杂志(电子版), 2022, 15(05): 637-642.
[9] 李青霖, 宋仁杰, 周飞虎. 一种重型劳力性热射病相关急性肾损伤小鼠模型的建立与探讨[J]. 中华肾病研究电子杂志, 2023, 12(05): 265-270.
[10] 姜金玉, 张东蕾, 何伟. 蓝光照射氧化损伤模型在眼部疾病中应用的研究进展[J]. 中华眼科医学杂志(电子版), 2022, 12(03): 168-172.
[11] 夏金根, 胡诗雨. 体外二氧化碳清除技术的重症应用场景[J]. 中华重症医学电子杂志, 2023, 09(01): 40-45.
[12] 路明, 杨博, 刘扬, 王慧, 洪文, 黄克林, 刘青. 肛门失禁大动物模型的建立[J]. 中华临床医师杂志(电子版), 2022, 16(04): 356-361.
[13] 李世凯, 梁佳, 何艳艳, 于毅, 李天晓, 常金龙, 贺迎坤. 兔颈动脉粥样硬化性狭窄模型在介入治疗的应用进展[J]. 中华介入放射学电子杂志, 2023, 11(04): 357-362.
[14] 高飞, 李惠凯, 冯秀雪, 杜晨, 韩珂, 柴宁莉, 令狐恩强. 3%聚桂醇消融动物囊性肿瘤模型的有效性和安全性研究[J]. 中华胃肠内镜电子杂志, 2023, 10(01): 31-36.
[15] 李宁, 刘言, 林慧庆. 肺移植供肺缺血再灌注损伤的机制及预防[J]. 中华胸部外科电子杂志, 2023, 10(04): 247-256.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号