Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb/c mice

Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb/c mice
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DOI:
10.1016/j.intimp.2011.04.011
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发表时间:
2011-09-01
影响因子:
5.6
通讯作者:
Fan, Yi-Ming
Fan, Yi-Ming
中科院分区:
医学2区
文献类型:
--
作者:
Huyan, Xiao-Hui;Lin, Ying-Ping;Fan, Yi-Ming

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环磷酰胺(cyclophosphamide,CTX)致免疫抑制动物模型的建立缺乏统一的标准,CTX对啮齿类动物外周血淋巴细胞亚群的免疫抑制作用尚缺乏相关资料。本文通过建立环磷酰胺诱导的小鼠模型,为真菌致病性的研究提供一种可行的免疫抑制模型。Balb/c小鼠以2天间隔接受两次不同CTX剂量(50-200 mg/kg)的腹膜内注射。于注射CTX前后不同时间点采集外周血,分别用全自动血细胞分析仪和流式细胞仪检测白色细胞(WBC)、淋巴细胞及其亚群。除CTX 50(50 mg/kg CTX)组外,其余各组的WBC和淋巴细胞在CTX处理后第1天开始呈剂量依赖性下降,第4天达到最低点,第10天回升,第17天再次下降。低剂量(50 mg/kg)CTX对CD 3(+)、CD 4(+)、CD 8(+)T细胞和CD 19(+)细胞的百分率无明显影响,而高剂量(100或150 mg/kg)CTX使CD 3(+)、CD 4(+)T细胞在第4天显著下降,CD 19(+)细胞在第10天显著下降,CD 8(+)细胞在第4天显著升高。CD 4(+)/CD 8(+)比值在第4天下降,随后在用3种不同剂量的CTX治疗时反弹。结果表明,以150 mg/kg CTX腹腔注射,间隔2 d,可建立Balb/c小鼠免疫抑制模型,用于研究真菌致病性。(C)2011 Elsevier B. V.保留所有权利。
There has been lack of the uniform standard for establishment of animal immunodepressive models induced by cyclophosphamide (CTX), and the information about the immunosuppressive effect of CTX on peripheral blood lymphocyte subsets in rodents. Here we describe a CTX-induced mouse model and try to establish a feasible immunosuppressive model for studying the fungal pathogenicity. Balb/c mice received two intraperitoneal injections of different CTX doses (50-200 mg/kg) at 2-day intervals. Peripheral whole blood collected at different time-points before and after CTX injection was used to detect white blood cells (WBCs), lymphocytes and their subsets by automated hematology analyzer and flow cytometry, respectively. WBCs and lymphocytes in all groups except CTX50 (50 mg/kg CTX) group commenced to decrease in a dose-dependent manner on day 1, reached the nadir on day 4, rebounded on day 10, and declined again on day 17 after CTX treatment. Low dose (50 mg/kg) CTX produced no obvious change of percentage of CD3(+),CD4(+) and CD8(+) T cells and CD19(+) cells, but high doses (100 or 150 mg/kg) yielded a significant decrease of CD3(+) and CD4(+) cells on day 4 and CD19(+) cells on day 10, and increase of CD8(+) cells on day 4. The CD4(+)/CD8(+) ratio decreased on day 4, followed by a rebound thereafter when treated with 3 different doses of CTX. The results indicate that two intraperitoneal injections of CTX at 150 mg/kg at 2-day intervals may establish good immunosuppressive models of Balb/c mice for studying the fungal pathogenicity. (C) 2011 Elsevier B.V. All rights reserved.