【Animal modeling】-Effect of busulfan on peripheral blood cells and bone marrow cells of type 2 diabetic KKAy mice

  Objective: To observe the damage effect of busulfan on the function of hematopoietic system in KK/upj-Ay/J(KKAy) mice, which is a model of type 2 diabetes mellitus, and compare it with the control C57BL/6J(B6) mice.

  Methods: Male KKAy mice were randomly divided into busulfan administration group and solvent control group. The former was injected with busulfan intraperitoneally at a dose of 40 mg/kg, and the latter was injected with the same dose of 5% DMSO. B6 mice were treated in the same way. grouping. After 15 days of administration, the mice were weighed, the immune organ coefficient was calculated, the peripheral blood count and classification of the mice were detected, and flow cytometry was used to detect hematopoietic progenitor cells (HPC), hematopoietic stem cells (HSC) and long-term hematopoietic cells in the bone marrow. The proportion of stem cells (longterm-hematopoieticstemcell, LT-HSC). The function of mouse hematopoietic progenitor cells was evaluated by a colony-forming unit-granulocyte and macrophage (CFU-GM) assay.

  Results: 15d after busulfan administration, the body weight, white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), blood platelet (PLT), lymphocyte (LYM) of KKAy mice were measured. ), neutrophil (NEU), the proportion of HPC, HSC and LT-HSC in bone marrow were significantly decreased, the number of CFU-GM was significantly decreased, and the proportion of spleen and thymocytes did not change significantly. After busulfan administration, the WBC, RBC, HGB and LYM of KKAy mice were significantly lower than those of B6 mice, but the ratio of PLT and HSC was significantly higher than that of B6 mice. The reduction of PLT and HSC in KKAy mice was significantly lower than that in B6 mice, while the reduction in HPC was significantly higher than that in B6 mice.

  Conclusion: 40mg/kg busulfan administration can damage the hematopoietic system function of mice. After busulfan administration, WBC, RBC, HGB, and LYM were more severely damaged in KKAy mice, but PLT and HSC were less damaged and more tolerant, while hematopoietic progenitor cells were less tolerant than B6 mice.