Effects Of Radiotherapy And Chemotherapy On The Hematopoietic Immune System Functions In T2DM Mice

Objective:Type 2 Diabetes Mellitus(T2DM)and malignant tumors share common risk factors,such as race,sex,age,lifestyle and etc.At present,the prevalence of malignant tumors with type 2 diabetes continues to rise.In the treatment of malignant tumors,the hematopoietic immune function of patients often becomes an important factor restricting the treatment.It has been found that T2DM affects the function of hematopoietic immune system.Therefore,the purpose of this study is to explore the differences of hematopoietic immune system function damages between T2DM and healthy mice after radiotherapy and chemotherapy,so as to provide more evidence-based medical evidence for the treatment of malignant tumors with diabetes mellitus,and bring more benefits to patients.Contents:The total body irradiation(TBI)injury model of KK/upj-Ay/J(KKAy)mice with T2DM and busulfan(BUS)chemotherapy injury model were used to observe the effects of radiotherapy and chemotherapy on hematopoietic immune system function,and compared with C57BL/6J(B6)mice.The difference of radiation sensitivity of mice cells was detected by X-ray irradiation in vitro.Methods:Male KKAy mice were rando mLy divided into irradiation group and control group.The mice in TBI group were irradiated by total body X-ray iradiation at a dose of 4 Gy.The control group received false irradiation and compared with B6 mice.KKAy mice were divided into vehicle control group and busulfan group.Busulfan 40 mg/kg was intraperitoneally injected into the busulfan group,5%DMSO was injected into the vehicle control group,and compared with B6 mice.15 days after irradiation or busulfan treatment,the immune organ coefficients were weighed and calculated.The peripheral blood routine of mice was measured.The proportion of hematopoietic progenitor cells(HPC),hematopoietic stem cells(HSC)and long-term hematopoietic stem cells(LT-HSC)in bone marrow,B cells and T cells in spleen were detected by flow cytometry.The function of HPC in mice was evaluated by colony forming unit-granulocyte and macrophage assay(CFU-GM).In order to detect the sensitivity of mouse bone marrow,spleen and thymus cells to X-ray exposure,mice cells were irradiated with 1 Gy and 4 Gy X-rays in vitro.Cell Titer-Glo lu minescence method was used to detect cell viability 12 hours later.Results:1)The hematopoietic immune system index of KKAy mice showed that the proportion of NEU%and HSC in KKAy mice was significantly lower than that in B6 mice(P<0.05),and NEU%was significantly higher than that in B6 mice(P<0.05).2)After 4 Gy total body irradiation,WBC,RBC,PLT,HGB and LYM in peripheral blood of KKAy mice decreased significantly(P<0.05);the proportion of HPC,HSC and LT-HSC in bone marrow decreased significantly(P<0.05);the proportion of spleen B cells and T cells decreased significantly(P<0.05);the proportion of thymus CD4CD8 double positive cells decreased significantly(P<0.05).The decrease level of bone marrow HSC,LT-HSC,peripheral blood RBC and HGB in KKAy mice was significantly lower than that in B6 mice(P<0.05).3)In vitro,12 hours after 1 Gy and 4 Gy X-ray irradiation,the survival rate of spleen and thymus cells in KKAy mice was significantly higher than that in B6 mice(P<0.05);after 12 hours of 4 Gy X-ray irradiation,the survival rate of bone marrow cells in KKAy mice was significantly lower than that in B6 mice(P<0.05).4)After busulfan treatment,the weight of KKAy mice,the ratio of spleen to brain,WBC,RBC,PLT,LYM,NEU,HPC,HSC and LT-HSC in bone marrow were significantly decreased(P<0.05).After busulfan treatment,WBC,RBC,HGB and LYM of KKAy mice were significantly lower than those of B6 mice(P<0.05),but the proportion of PLT and HSC was significantly higher than that of B6 mice(P<0.05).The decrease of PLT and HSC in KKAy mice was significantly lower than that in B6 mice,while the decrease of HPC was significantly higher than that in B6 mice(P<0.05).Conclusion:There are differences in hematopoietic immune system between KKAy mice and B6 mice,mainly in the index of NEU%and HSC%in bone marrow;4 Gy total body irradiation damages the function of hematopoietic immune system in KKAy mice;KKAy mice may be more tolerant to ionizing radiation than B6 mice in HGB,PLT,HSC and LT-HSC.Spleen and thymus cells of KKAy mice in vitro are more sensitive to X-ray.The sensitivity of bone marrow cells was higher than that of B6 mice.The difference of tolerance to ionizing radiation between KKAy mice and B6 mice may be related to the microenvironment in vivo and the radiation sensitivity of cells themselves.40 mg/kg busulfan can damage the function of hematopoietic immune system of mice.After busulfan treatment,WBC,RBC,HGB and LYM of KKAy mice were severely damaged,but PLT and HSC were mildly damaged and more tolerant,while the tolerance of hematopoietic progenitor cells was lower than that of B6 mice.