热灭活的大肠埃希菌促进照射后小鼠粒系造血及生存

Heat-inactivated E.coli promotes granulocytic hematopoiesis and survival of mice after irradiation

目的:本研究应用热灭活的大肠埃希菌(HI E.coli)模拟急性腹腔炎症,观察和分析该预处理方案对照射后小鼠造血恢复的影响,以期探索出一种促进放疗后免疫系统,尤其是粒系重建的新策略。方法:通过给小鼠腹腔注射HI E.coli建立急性腹腔炎症模型;运用不同剂量X射线照射已诱发腹腔炎症的小鼠,并定期观察小鼠的生存质量;通过流式细胞仪检测脾脏、骨髓内各血细胞的比例,分析照射后小鼠造血和免疫系统,尤其是粒系恢复的情况。结果:HI E.coli预处理提高了致死剂量(7 Gy)照射后小鼠的生存率,其中对照组死亡率为100%,而HI E.coli预处理实验组死亡率仅为14%,即死亡率降低了86%(P=0.0003)。此外,应用非致死剂量(4 Gy)观察照射后小鼠造血系统的恢复,发现在照射后第7天,外周血、脾脏、骨髓中的各阶段粒系细胞(粒系-巨噬系祖细胞,原始粒细胞,早幼粒细胞,中幼粒细胞,晚幼粒细胞,杆状核和分叶核粒细胞)相比于对照组均有明显增多(P<0.05),其中粒系-巨噬系祖细胞最为明显(P<0.001)。结论:照射前应用HI E.coli预处理可促进小鼠的造血恢复,尤其促进了粒系重建。其机制为HI E.coli诱导的小鼠体内急性炎症微环境影响了骨髓造血干/祖细胞,尤其是粒系-巨噬系祖细胞,促进照射后小鼠粒系的恢复,提高了照射后小鼠的生存率。

Objective:The work demonstrated the effect of heat-inactivated E.coli(HI E.coli)on the recovery of immune system,especially the recovery of granulocyte series after irradiation in mice and provided new idea for treatment of patients post irradiation.Methods:Acute peritoneal cavity inflammation model induced by HI E.coli and irradiation model were used to study the immune system,especially the granulocyte series recovery.Also,different cell types were mainly analyzed by flow cytometry(surface and cytoplasm markers).Results:HI E.coli improved the survival of mice post irradiation(7 Gy),the case fatality rate of control group was 100%,but the HI E.coli group was only 14%.The case fatality rate was reduced by 86%(P=0.0003).In addition,7 days after irradiation with lower dose(4 Gy)the recovery of hematopoietic organs,including peripheral blood,spleen,bone marrow,were better than control group.The granulocyte-macrophage progenitor cell(GMP),myeloblast,promyelocyte,myelocyte,metamyelocyte,band cell and segmented cell in bone marrow were significantly increased(P<0.05)compared with the control group,especially GMP(P<0.001).Conclusion:The acute inflammation induced by HI E.coli can promote the production and differentiation of granulocytes through acting on GMP,so as to improve the survival rate of irradiated mice.