关键词: 环磷酰胺, 免疫抑制, 小鼠

Abstract: Objective The aim of present study is to compare the effects of four different modeling method of cyclophosphamide on the immune function of mice. Method Four different ways were employed to develop immunocompromised mouse models by cyclophosphamide, Group A: mice were intraperitoneally injected with cyclophosphamide 80 mg / kg on days 1, 3, and 5, Group B: mice were intraperitoneally injected with cyclophosphamide 60 mg / kg for 5 consecutive days, Group C: mice were intraperitoneally injected with cyclophosphamide 60 mg / kg on days 1, 3, 5, 7, 9, 11 and 13, Group D: mice were intraperitoneally injected with cyclophosphamide 60 mg / kg on days 1, 4, 7, 10 and 13) . The general immunological indexes of mice ( body weight, thymus index, spleen index, whole blood leukocyte and lymphocyte count ) , cellular immunity ( delayed allergic reaction ) and humoral immunity ( determination of half hemolysis value) were observed and compared in the four different models. Result In each experimental group, the relevant detection indexes changed in varying degrees. Compared with the blank control group, the body mass, thymus index, spleen index and WBC count of mice in experimental group A and model group decreased by 19. 15%, 67. 69%, 67. 59% and 83. 87% respectively on the 7th day, while the body mass of mice in model group decreased by 17. 91%, while the thymus index, spleen index and WBC count increased by 7. 14%, 173. 89% and 67. 76% respectively on the 14th day; Compared with the blank control group, the body mass, thymus index and spleen index of mice in experimental group B and model group decreased by 15. 64%, 64. 91% and 64. 60% respectively on the 7th day, and the body mass and thymus index of mice in model group decreased by 17. 86% and 48. 00% respectively on the 14th day, while the spleen index increased by 148. 80%; Compared with the blank control group, the body mass, thymus index, spleen index, WBC count and lymphocyte count of mice in experimental group C and model group decreased by 11. 74%, 82. 61%, 37. 42%, 88. 40% and 91. 44% respectively; Compared with the blank control group, the body mass, thymus index, spleen index, whole blood leukocyte count and lymphocyte count of mice in experimental group D and model group decreased by 10. 83%, 68. 31%, 14. 34%, 66. 15% and 73. 42% respectively. In DTH experiment, the weight difference between left and right ears of immunosuppressive mice decreased by 66. 88%, and in humoral immunity, the serum HC50 of immunosuppressive mice decreased by 74. 52%. In the experiments of group A and B, the relevant detection indexes recovered in varying degrees on the 14th day compared with the 7th day. Meanwhile, the immunosuppressive state of group A mice was more serious in the short term, while the immunosuppressive state of group B mice remained more lasting. Conclusion The above four method could successfully establish immunosuppressive model in mice, and the times, dose, interval days of intraperitoneal injection of cyclophosphamide and the detection endpoint will affect the effect of the immunosuppressive state of mice. So the appropriate model can be selected according to the specific evaluation requirements of drugs.

Key words: cyclophosphamide, immunosuppression, mice