去铁胺促进亚致死剂量X射线辐照小鼠的骨髓造血功能恢复  

Deferoxamine promotes recovery of bone marrow hematopoietic function in mice exposed to a sublethal dose of X-ray irradiation

作　　者：张小敏 吴泽彬 蓝惠璇 陈姗姗 吴杰 朱玲玲[2,3] 肖扬 ZHANG Xiaomin;WU Zebin;LAN Huixuan;CHEN Shanshan;WU Jie;ZHU Lingling;XIAO Yang(Department of Hematology,Jinshazhou Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510168,China;College of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China;Department of Hematology,Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510000,China;Department of Hematology,Shenzhen Qianhai Shekou Pilot Free Trade Zone Hospital,Shenzhen 518067,China)

机构地区：[1]广州中医药大学金沙洲医院,血液科,广东广州510168 [2]南方医科大学中医药学院,广东广州510515 [3]南方医科大学中西医结合医院血液科,广东广州510000 [4]深圳市前海蛇口自贸区医院血液科,广东深圳518067

出　　处：《南方医科大学学报》2023年第9期1577-1584,共8页Journal of Southern Medical University

基　　金：国家自然科学基金(81873426,81973583);广东省自然科学基金(2021A1515011575);深圳市科技计划项目(JCYJ20220530151613030)。

摘　　要：目的探讨去铁胺(DFO)对亚致死剂量X射线辐照C57小鼠骨髓造血功能的影响。方法将C57小鼠随机分成空白对照组、全身亚致死剂量辐照组(TBI组)、DFO治疗组(DFO组),每组10只。经5.4 Gy、1.0 Gy/min X射线全身辐照后,DFO组小鼠每天经皮下注射给予100 mg·kg-1 DFO溶液,其余各组小鼠皮下注射等量的生理盐水。每隔2 d称小鼠体质量,给药10 d后每组随机处理5只小鼠,检测血细胞计数、骨髓有核细胞计数、骨髓CD34+细胞比例及骨髓有核细胞中凋亡、铁死亡相关蛋白cleaved PARP-1、cleaved caspase-3、血管内皮生长因子(VEGF)、GPX4及SLC7A11的表达;给药20 d后处理每组剩余的5只小鼠,分别检测血细胞计数、骨髓有核细胞计数、骨髓病理学等。结果与空白对照组相比,TBI组和DFO组小鼠体质量在第3天明显降低(P<0.05),第6天TBI组小鼠体质量降至最低(P<0.01)。与空白对照组相比,在辐照后第10、20天TBI组小鼠血细胞计数、骨髓有核细胞计数明显降低(P<0.01或P<0.001),骨髓病理显示TBI组小鼠骨髓造血组织及有核细胞明显减少、出现脂肪空泡等,并且在辐照后第10天TBI组小鼠骨髓有核细胞中cleaved PARP-1和cleaved caspase-3蛋白表达明显增加(P<0.01),而GPX4、SLC7A11蛋白表达明显减少(P<0.05)。与TBI组相比,在辐照后第10天DFO组小鼠骨髓中CD34+细胞比例明显增加(P<0.001);骨髓中cleaved PARP-1和cleaved caspase-3蛋白表达明显降低(P<0.05),GPX4、SLC7A11蛋白表达明显增加(P<0.05),及骨髓微环境中VEGF表达增加(P<0.05);与TBI组相比,在辐照后第20天DFO组白细胞、红细胞、血小板、骨髓有核细胞计数明显升高(P<0.05或P<0.01),并且骨髓病理显示骨髓造血组织及有核细胞增加。结论DFO可能通过抑制骨髓有核细胞凋亡、铁死亡,并促进骨髓微环境中VEGF表达及CD34+细胞增殖来改善亚致死剂量辐照小鼠骨髓造血功能。Objective To evaluate the effect of deferoxamine(DFO)on bone marrow hematopoietic function in C57 mice exposed to a sublethal dose of X-ray irradiation.Methods C57 mice exposed to a sublethal dose(5.4 Gy,1.0 Gy/min)of total body X-ray irradiation(TBI)were treated with subcutaneous injection of 100 mg/kg DFO,with normal saline as the control,on a daily basis for 10 and 20 consecutive days.Body weight changes of the mice were monitored every 3 days.Five mice were selected from each group at 10 and 20 days for examination of blood cell counts,bone marrow nucleated cell counts,percentage of bone marrow CD34+cells,bone marrow pathology,and expressions of cleaved PARP-1,cleaved caspase-3,VEGF,GPX4,and SLC7A11 in the nucleated cells.Results The body weight of the mice decreased significantly on day 3 in TBI and DFO groups(P<0.05),and to the lowest on day 6 in TBI group(P<0.01).Blood cell counts and bone marrow nucleated cell counts of the mice were significantly decreased at 10 and 20 days following TBI(P<0.01).On day 10 following TBI,the mice showed significantly decreased nucleated cells and the presence of adipocytes in the bone marrow,where increased expressions of cleaved PARP-1 and cleaved caspase-3 and lowered expressions of GPX4 and SLC7A11 were detected in the nucleated cells(P<0.05).In the mice exposed to TBI,treatment with DFO significantly increased CD34+cell percentage(P<0.001),decreased the expressions of cleaved PARP-1 and cleaved caspase-3,and increased the expressions of GPX4,SLC7A11 and VEGF in the bone marrow nucleated cells(P<0.05).DFO treatment significantly increased blood cell counts and bone marrow nucleated cells in mice at 20 days following TBI(P<0.05).Conclusion DFO improves bone marrow hematopoiesis in mice with sublethal-dose TBI by inhibiting apoptosis and ferroptosis of bone marrow nucleated cells and promoting VEGF expression and CD34+cell proliferation.

关 键 词：去铁胺 亚致死剂 X射线 骨髓造血 血管内皮生长因子 

分 类 号：R818[医药卫生—放射医学]