甲氨蝶呤联合环磷酰胺对大鼠骨髓和外周血淋巴细胞细胞周期和周期蛋白D1作用的研究  

Study of the effect of methotrexate and cyclophophamide on cell cycle and cyclin D1 of lymphocytes in the periphery blood and bone marrow in rats

作　　者：茹晋丽[1] 李小峰[1] 王鑫[1] 牛红青 张莉芸[1] 

机构地区：[1]山西医科大学第二医院风湿免疫科,太原030001 [2]中华风湿病学杂志社

出　　处：《中华风湿病学杂志》2009年第8期541-544,共4页Chinese Journal of Rheumatology

基　　金：山西省自然科学基金（2007011116）;山西省卫生厅科技攻关项目（200614）

摘　　要：目的探讨甲氨蝶呤（MTX）、环磷酰胺（CTX）联合给药对骨髓和外周血淋巴细胞（PBL）细胞周期及细胞周期蛋白（cvclin）的交互作用。方法健康Wistar大鼠随机分为4个实验组：健康对照组、MTX组、CTX组和联合组（MTX＋CTX）。在给药前、给药后3、9、18、27周后分别采血，流式细胞术（FCM）检测PBL的细胞周期及cvclin D1。在给药后上述时点检测骨髓淋巴细胞的细胞周期及cvclin D1。结果①MTX组，PBL的S期细胞比例明显低于其他各组（P〈0．05）。骨髓淋巴细胞G0／G1期细胞比例有增高趋势，而S期细胞比例有下降趋势。CTX组对细胞各期比例的影响差异无统计学意义。联合组，PBL和骨髓淋巴细胞G0／G1期细胞比例下降，而S期细胞比例升高（P〈0．05）。不同解剖时点间比较差异无统计学意义。②对PBL和骨髓淋巴细胞的cvclin D1表达的影响，不同用药组间、不同解剖时点间比较差异无统计学意义。结论①MTX、CTX联合用药对正常大鼠PBL和骨髓细胞周期的影响存在拮抗作用，最终阻止了细胞增殖周期的进程。②MTX、CTX联合给药对PBL和骨髓淋巴细胞周期的影响并非通过cvclin D1途径来实现。Objective To investigate the synergistic effect of methotrexate （MTX） and cyclophos phamide （CTX） on cell cycle and cyclin DI of periphery blood lymphocytes （PBLs） and bone marrow byflow cytometry. Methods Wistar rats were randomly divided into four groups including normal control, MTX and cyclophosphamide combination group, MTX and CTX only treatment groups respectively. PBLs were isolated for flowcytometry analysis for the changes of cell cycle and the expression of cyclin D1 at week 0, week 3,week 9, week18 and week 27. Mice were dissected and the changes of lymphocytes cell cycle and the expressions of cyclin D1 in the bone marrow were measured at week 0, week 3, week 9, week 18 and week 27 after treatment by FCM. Results ① In the MTX treatment group, the percentage of phase S cells was evidently lower than other groups in the PBLs （P〈0.05）. In the bone marrow, the phase G0/G1 cells of lymphocytes were increased and the ratio of phase S cells was decreased （P〉0.05）. In the CTX treatment group, there was no statistical difference in ratios of each phase. In the MTX and CTX combination treatment group, the proportion of phase G0/G1 cells decreased significantly and the percentage of phase S cells increased in both PBLs and bone marrow cells （P〈0.05）. And there was no statistical significant difference in different time points after treatment. ② There was no statistical significant difference in the expression of cyclin DI in PBLs and bone marrow between different groups or different dissecting time points. Conclusion MTX combined with CTX has been shown to have antagonistic effect on cell cycle. However, this effect is not via the cyclin D1 pathway.

关 键 词：环磷酰胺 甲氨蝶呤 细胞周期 细胞周期蛋白D1 大鼠 Wistar 

分 类 号：R686[医药卫生—骨科学]