~(137)Cs γ射线联合环磷酰胺与氯霉素介导的获得性再生障碍性贫血小鼠模型的建立
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摘要
目的:对γ射线(~(137)Cs)联合环磷酰胺与氯霉素介导的获得性再生障碍性贫血小鼠模型进行改进研究,为再生障碍性贫血发病机制和治疗的研究提供稳定模型。方法:BALB/c小鼠经3-5 Gy~(137)Csγ射线(91 cGy/min)照射后,于d 4、5、6腹腔注射环磷酰胺25 mg/(kg·d)、氯霉素62. 5 mg/(kg·d),观察其外周血白细胞计数、网织红细胞计数、骨髓涂片及骨髓有核细胞计数、骨髓病理切片等指标。结果:经~(137)Csγ射线照射联合环磷酰胺、氯霉素腹腔注射的BALB/c小鼠的外周血三系细胞均迅速减少,其中白细胞、血小板、网织红细胞表现得尤为明显;于d14降至最低,在d 28三系细胞仍然严重减少,骨髓有核细胞数量明显下降,骨髓增生程度呈减低或重度减低;骨髓病理切片示造血细胞重度减少;脂肪细胞等非造血细胞增多。结论:通过~(137)Csγ射线照射并联合环磷酰胺、氯霉素腹腔注射的小鼠模型,其各项检测指标均达到获得性再生障碍性贫血的诊断标准,可作为获得性再生障碍性贫血发病机制及治疗研究的小鼠模型。
Objective: To improve and establish the mouse model w ith aplastic anemia( AA) mediated by~(137) Cs γ-ray irradiation combined w ith cyclophosphamide( CTX) and chloramphenicol( CHL) injection,so as to provide a stable model for studying the pathogenesis and treatment of AA. Methods: The BALB/c mice w ere exposed to~(137) Cs γ-ray of3-5 Gy( 91 cG y/min) and w ere intraperitoneally injected w ith CTX of 25 mg/( kg. d) and CHL of 62. 5 mg/( kg. d)at D 4,5 and 6 after irradiation; the WBC,platelet and reticulocyte counts in peripheral blood as w ell as the mucleated cell count in bone marrow and bone marrow smears w ere detected. Results: The 3-lineage cells in peripheral blood of BALB/c mouse model w ith acquired AA w ere rapidly reduced,especially WBC,platelet and reticulocyte counts w ere low est at D 14,the 3-lineage cells in peripheral blood w ere still severely reduced at D 28; the nucleated cell count in bone marrow significantly dcreased,the bone marrow hyperplasia w as reduced or severely reduced; the pathological sections of bone marrow show ed the severe reduction of hematopoietic cells and the increased of non-hematopoietic cells such as fat cells. Conclusion: The mouse model w ith acquired AA has been established by~(137) Csγ-ray irradiation combined w ith CTX and CHL injection. All detection indicators of this model reach to diagnostic criteria for acquired AA,therefore this mouse model may be used as the model for study of pathogenesis and treatment of acquired AA.
Objective: To improve and establish the mouse model w ith aplastic anemia( AA) mediated by~(137) Cs γ-ray irradiation combined w ith cyclophosphamide( CTX) and chloramphenicol( CHL) injection,so as to provide a stable model for studying the pathogenesis and treatment of AA. Methods: The BALB/c mice w ere exposed to~(137) Cs γ-ray of3-5 Gy( 91 cG y/min) and w ere intraperitoneally injected w ith CTX of 25 mg/( kg. d) and CHL of 62. 5 mg/( kg. d)at D 4,5 and 6 after irradiation; the WBC,platelet and reticulocyte counts in peripheral blood as w ell as the mucleated cell count in bone marrow and bone marrow smears w ere detected. Results: The 3-lineage cells in peripheral blood of BALB/c mouse model w ith acquired AA w ere rapidly reduced,especially WBC,platelet and reticulocyte counts w ere low est at D 14,the 3-lineage cells in peripheral blood w ere still severely reduced at D 28; the nucleated cell count in bone marrow significantly dcreased,the bone marrow hyperplasia w as reduced or severely reduced; the pathological sections of bone marrow show ed the severe reduction of hematopoietic cells and the increased of non-hematopoietic cells such as fat cells. Conclusion: The mouse model w ith acquired AA has been established by~(137) Csγ-ray irradiation combined w ith CTX and CHL injection. All detection indicators of this model reach to diagnostic criteria for acquired AA,therefore this mouse model may be used as the model for study of pathogenesis and treatment of acquired AA.
引文
1沈秀,张荷清,吴美羔,等.137Csγ射线亚致死剂量照射小鼠生物学效应的研究.中国辐射卫生,2004;13(4):245-247.
2 Shao L,Feng W,Li H,et al.Total body irradiation causes longterm mouse BM injury via induction of HSC premature senescence in an Ink4a-and Arf-independent manner.Blood,2014;123(20):3105-3115.
3 Shao L,Luo Y,Zhou D.Hematopoietic stem cell injury induced by ionizing radiation.Antioxid Redox Sign,2014;20(9):1447-1462.
4 Krosniak M,Papiez MA,Kaczmarczyk J,et al.Influence of fructose and Fatty-Rich diet combined with vanadium on bone marrow cells.Biol Trace Elem Res,2013;155(2):276-282.
5 Da WM.In vitro studies on the pathogenesis of aplastic anemia in Chinese patients.Exp Hematol,1988;16(5):336-339.
6 Turton JA,Fagg R,Sones WR,et al.Characterization of the myelotoxicity of chloramphenicol succinate in the B6C3F1 mouse.Int JExp Pathol,2006;87(2):101-112.
7 Bloom ML,Wolk AG,Simon-Stoos KL,et al.A mouse model of lymphocyte infusion-induced bone marrow failure.Exp Hematol,2004;32(12):1163-1172.
8 Gaman A,Gaman G,Bold A.Acquired aplastic anemia:correlation between etiology,pathophysiology,bone marrow histology and prognosis factors.Rom J Morphol Embryol.2009;50(4):669-674.
9 Faiola B,Fuller ES,Wong VA,et al.Exposure of hematopoietic stem cells to benzene or 1,4-benzoquinone induces gender-specific gene expression.Stem Cells,2004;22(5):750-758.
10王焕新,张桂如.电离辐射与白细胞减少.北京:原子能出版社,1991;4.
11张擎,彭红娟,余晓彬,等.环磷酰胺诱发小鼠血小板减少症模型的建立及其血小板功能的测定.南方医科大学学报,2003;23(12):1277-1279.
12 Franco RS.Measurement of red cell lifespan and aging.Transfus Med Hemother,2012;39(5):302-307.
13 Triulzi D,Duquesnoy R,Nichols L,et al.Fatal transfusion-associated graft-versus-host disease in an immunocompetent recipient of a volunteer unit of red cells.Transfusion,2006;46(6):885-888.
14朱自严,陈和平,向东,等.环磷酰胺抑制作用下小鼠对人红细胞抗原的选择性耐受.临床输血与检验,2002;4(4):8-11.
15卢兴国.现代血液形态学理论与实践.上海:上海科学技术出版社,2003;94.
2 Shao L,Feng W,Li H,et al.Total body irradiation causes longterm mouse BM injury via induction of HSC premature senescence in an Ink4a-and Arf-independent manner.Blood,2014;123(20):3105-3115.
3 Shao L,Luo Y,Zhou D.Hematopoietic stem cell injury induced by ionizing radiation.Antioxid Redox Sign,2014;20(9):1447-1462.
4 Krosniak M,Papiez MA,Kaczmarczyk J,et al.Influence of fructose and Fatty-Rich diet combined with vanadium on bone marrow cells.Biol Trace Elem Res,2013;155(2):276-282.
5 Da WM.In vitro studies on the pathogenesis of aplastic anemia in Chinese patients.Exp Hematol,1988;16(5):336-339.
6 Turton JA,Fagg R,Sones WR,et al.Characterization of the myelotoxicity of chloramphenicol succinate in the B6C3F1 mouse.Int JExp Pathol,2006;87(2):101-112.
7 Bloom ML,Wolk AG,Simon-Stoos KL,et al.A mouse model of lymphocyte infusion-induced bone marrow failure.Exp Hematol,2004;32(12):1163-1172.
8 Gaman A,Gaman G,Bold A.Acquired aplastic anemia:correlation between etiology,pathophysiology,bone marrow histology and prognosis factors.Rom J Morphol Embryol.2009;50(4):669-674.
9 Faiola B,Fuller ES,Wong VA,et al.Exposure of hematopoietic stem cells to benzene or 1,4-benzoquinone induces gender-specific gene expression.Stem Cells,2004;22(5):750-758.
10王焕新,张桂如.电离辐射与白细胞减少.北京:原子能出版社,1991;4.
11张擎,彭红娟,余晓彬,等.环磷酰胺诱发小鼠血小板减少症模型的建立及其血小板功能的测定.南方医科大学学报,2003;23(12):1277-1279.
12 Franco RS.Measurement of red cell lifespan and aging.Transfus Med Hemother,2012;39(5):302-307.
13 Triulzi D,Duquesnoy R,Nichols L,et al.Fatal transfusion-associated graft-versus-host disease in an immunocompetent recipient of a volunteer unit of red cells.Transfusion,2006;46(6):885-888.
14朱自严,陈和平,向东,等.环磷酰胺抑制作用下小鼠对人红细胞抗原的选择性耐受.临床输血与检验,2002;4(4):8-11.
15卢兴国.现代血液形态学理论与实践.上海:上海科学技术出版社,2003;94.
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