| ObjectiveTo evaluate the effects of treatment combined recombinant human G-CSF (rhG-CSF) and recombinant human interleukin-11 (rhIL-11) on extremely severe acute hemopoietic radiation sickness beagles, and especially to explore the effects on hemopoietic function.Methods(1) Sixteen beagles were irradiated with 4.5Gy 60Coγ-ray to establish acute radiation sickness (ARS) models, and animals were randomly divided into three cohorts, i.e., irradiated control (n=5), supportive care (n=5) and combined cytokines treatment cohort (n=6). The irradiated control cohort was given no treatment, the supportive care cohort received purely symptomatic treatment contained blood transfusion and anti-infection while the combined cytokines treatment cohort received rhG-CSF 10μg·kg-1·d-1 and rhIL-11 50μg·kg-1·d-1 subcutaneously for tree weeks besides symptomatic treatment. Manifestation and characteristics of ARS beagles were observed, number of survival animals and survival time were recorded. At last, post-mortem examination and histological examination were performed.(2) Peripheral blood hemogram was examined once every two days, and bone marrow was collected to make smears to evaluate levels of bone marrow hyperplasia at 4 day before radiation and at 1day and 45 days after radiation.(3) Bone marrow and peripheral blood were collected to proceed hematopoietic progenitor colony cultivation, to count CD34+ cells, to detect cell apoptosis, necrosis, cycle, and to measure telomerase activity at 4 day before radiation and at 1day and 45 day after radiation.Results (1) After irradiation, all animals underwent nausea, diarrhea and fever. The mean blood transfusion volume of cytokines cohort and the period of blood transfusion all were less than supportive care cohort (P<0.01). The period of administrated antibiotic of cytokines cohort was shorter than supportive care cohort (P<0.05). In the observed period of 45 day, all of combined cytokines treatment beagles were survival, their haematopoiesis and gastrointestinal tract were recovered. The survivals of three cohorts were different (P<0.05).(2) All kinds of cells'population declined sharply, but rebounded to normal basically in combined cytokines treatment cohort. While after cytokines were administrated, the content of CD34+ cells in peripheral blood were markedly up-regulated at 1 day(P<0.05), and then maintained at a relatively high level after that. Bone marrow hyperplasia in combined cytokines treatment cohort was more active than in supportive care cohort at 45 day after irradiation(P<0.05).(3) In the early period after irradiation, G0/G1 phase blockage of nucleated cells in peripheral blood became more serious, the rate of apoptosis and necrosis of nucleated cells in peripheral blood were significantly lower than in irradiation control and symptomatic treatment cohorts (P<0.05). At 45 day after irradiation,the number of BFU-E of peripheral blood, CFU-Mix of bone marrow in combined cytokines cohort was all higher than in supportive care cohort (P<0.05), and the telomerase activity levels of bone marrow were also higher than supportive care cohorts (P<0.05).Conclusion(1) Administration of rhG-CSF and rhIL-11 early after irradiation and continued daily, in combined with supportive care on severe acute hemopoietic radiation sickness beagles could benefit hematopoietic function and gastrointestinal tract recovery, increase survival of irradiated canines and improve quality of life.(2) Improving hematopoietic hyperplasia and complete blood cells recovery by the usage of cytokines would mitigate the risks of hemorrhage and infection related to the period of BM aplasia, significantly decreased the need volume of blood transfusion, shorted the period of anti-infection.(3) The mechanism of cytokines curing hematopoietic injuries induced by irradiation could mobilize CD34+ cells in bone marrow to peripheral blood, keep G0/G1 phase blockage and reduce apoptosis, maintain relative higher level of telomerase activity, and maybe preserve propagation activity of hematopoietic stem/progenitor cells and promote hematopoietic function restoration.
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