BUCY预处理小鼠异基因骨髓移植后aGVHD模型的建立

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (1676 KB) HTML (0 KB)
输出: BibTeX | EndNote (RIS)

摘要目的：建立白消安（BU）联合环磷酰胺（CY）化疗预处理的小鼠异基因造血干细胞移植（allo-HSCT）后急性移植物抗宿主病（aGVHD）的小鼠动物模型。方法：BALB/C受鼠以BUCY方案化疗预处理，根据化疗剂量分3组：1～4 d分别予BU 35、38、40 mg·kg-1·d-1，5～6 d予CY 100 mg·kg-1·d-1，第8天尾静脉回输C57BL/6供鼠骨髓细胞（2×107个）和脾细胞（2×107个），移植后定期观察记录受鼠一般情况等以判断aGVHD 的程度。结果：BU剂量为40 mg·kg-1·d-1受鼠组小鼠移植后体质量进行性下降，移植后6 d内全部死亡。BU剂量为35 mg·kg-1·d-1受鼠组观察到轻微aGVHD的临床症状，小鼠长期存活。BU剂量为38 mg·kg-1·d-1受鼠组观察到典型aGVHD临床症状及病理改变。结论：经BUCY（BU 38 mg·kg-1·d-1+CY 100 mg·kg-1·d-1）方案预处理后回输异基因骨髓细胞（2×107个）和脾细胞（2×107个）能成功构建aGVHD实验动物模型。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	程婷婷1
	2
	周琳1
	梁彬1
	陈慧瑶1
	俞康1

关键词 ：移植物抗宿主病, 异基因造血干细胞移植, 化疗

Abstract：Objective: To establish an acute graft-versus-host disease experimental animal model after allogeneic hematopoietic were stem cell transplantation conditioned with busulfan (BU) and cyclophosphamide (CY). Methods: BALB/C Recipients were divided into three groups accarding to 3 different doses of BU (35, 38, 40 mg•kg-1•d-1) for 4 days, followed by CY (100 mg•kg-1•d-1) for 2 days. On the 8th day recipient mice received bone marrow cells (2×107) and splenocytes (2×107) from the C57BL/6 donors. All recipients were monitored daily after hematopoietic stem cell transplantation for clinical manifestations of aGVHD. Results: The recipients conditioned with BU of 40 mg•kg-1•d-1 exhibited progressive weight loss and all died within 6 days after reinfusion. The recipients received BU of 35 mg•kg-1•d-1 had no significant clinical manifestations of aGVHD with long-term survival. The recipients conditioned with BU dose of 38 mg•kg-1•d-1 exhibited severe aGVHD typical clinical symptoms and pathology manifestation. Conclusion: Through a BUCY-based conditioning regimen (BU 3 mg•kg-1•d-1+CY 100 mg•kg-1•d-1) together with the reinfusion of bone marrow cells (2×107) and splenocytes (2×107), aGVHD experimental animal model can be established.

Key words： graft-versus-host disease allogeneic hematopoietic stem cell transplantation chemotherapy

收稿日期: 2014-11-04

基金资助:国家自然科学基金资助项目（81172613）；浙江省自然科学基金资助项目（Y12H080012，Y2101069）。

通讯作者: 俞康，教授，博士生导师，Email：yukang602@126.com。

作者简介: 程婷婷（1987-），女，湖北襄阳人，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2015/V45/I7/479

[1] Stelljes M, Beelen DW, Braess J, et al. Allogeneic transplantation as post-remission therapy for cytogenetically high-risk acute myeloid leukemia: landmark analysis from a single prospective multicenter trial[J]. Haematologica, 2011, 96(7): 972-979.
[2] Pavlu J, Szydlo RM, Goldman JM, et al. Three decades of transplantation for chronic myeloid leukemia: what have we learned?[J]. Blood, 2011, 117(3): 755-763.
[3] Lee SJ. New approaches for preventing and treating chronic graft—versus-host disease[J]. Blood, 2005, 105(11): 4200-4206.
[4] Hill GR, Crawford JM, Cooke KR, et al. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines[J]. Blood, 1997, 90(8): 3204-3213.
[5] Cao T, Soto A, Zhou W, et al. Ex vivo expanded human CD4+CD25+Foxp3+regulatory T cells prevent lethal xenogenic graft versus host disease (GVHD)[J]. Cell Immunol,2009, 258(1): 65-71.
[6] Sadeghi B, Aqhdami N, Hassan Z, et al. GVHD after chemotherapy conditioning in allogeneic transplanted mice[J]. Bone Marrow Transplant, 2008, 42(12): 807-818.
[7] Cooke KR, Kobzik L, Martin TR, et al. An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin[J]. Blood, 1996, 88(8): 3230-3239.
[8] Speiser DE, Bachmann MF, Shahinian A, et al. Acute graftversus-host disease without costimulation via CD28[J]. Transplantation,1997, 63(7): 1042-1044.
[9] Blazar BR, Murphy WJ, Abedi M. Advances in graft-versus-host disease biology and therapy[J]. Nat Rev Immunol, 2012, 12(6): 443-458.
[10] Lappas CM, Liu PC, Linden J, et al. Adenosine A2A receptor activation limits graft-versus-host disease alter allogenic hematopoietic stem cell transplantation[J]. J Leukoc Biol,2010, 87(2): 345-354.
[11] Ramkumar V, Hallam DM, Nie Z. Adenosine oxidative stress and cytoprotection[J]. Jpn J Pharmacol, 2001, 86(3):265-274.
[12] Blazar BR, Murphy WJ. Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD)[J]. Philos Trans R Soc Lond B Biol Sci, 2005, 360(1461):1747-1767.
[13] Korngold R, Sprent J. Graft-versus-host disease in experimental allogeneic bone marrow transplantation[J]. Proc Soc Exp Biol Med, 1991, 197(1): 12-18.
[14] Dutt S, Ermann J, Tseng D, et al. L-selectin and beta7 integrin on donor CD4 T cells are required for the early migration to host mesenteric lymph nodes and acute colitis of graft-versus-host disease[J]. Blood, 2005, 106(12): 4009-4015.
[15] Rosset MB, Tieng V, Charron D, et al. Differences in MHC-class I presented minor histocompatibility antigens extracted from normal and graft-versus-host disease (GVHD) mice[J].Clin Exp Immunol, 2003, 132(1): 46-52.
[16] Ferrara J, Guillen FJ, Sleckman B, et al. Cutaneous acute graft-versus-host disease to minor histocompatibility antigens in a murine model: histologic analysis and correlation to clinical disease[J]. J Invest Dermatol, 1986, 86(4): 371-375.
[17] Nash RA, Pepe MS, Storb R, et al. Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate[J]. Blood, 1992, 80(7): 1838-1845.
[18] Ploemacher RE, Johnson KW, Rombouts EJ, et al. Addition of treosulfan to a nonmyeloablative conditioning regimen results in enhanced chimerism and immunologic tolerance in an experimental allogeneic bone marrow transplant model [J]. Biol Blood Marrow Transplant, 2004, 10(4): 236-245.
[19] 蔡芳芳, 俞康, 江松福. 小鼠同种异基因骨髓移植aGVHD动物模型的建立[J]. 温州医学院学报, 2009, 39(4): 320-324.
[20] 杨志刚, 曾耀英, 王青, 等. 小鼠异基因骨髓移植急性移植物抗宿主病模型的建立[J]. 中国病理生理杂志, 2004, 20 (10): 1947-1949.