南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (9): 1577-1584.doi: 10.12122/j.issn.1673-4254.2023.09.15

• • 上一篇    下一篇

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

张小敏，吴泽彬，蓝惠璇，陈姗姗，吴 杰，朱玲玲，肖 扬   

  1. 广州中医药大学金沙洲医院，血液科，广东 广州 510168；南方医科大学中医药学院，广东 广州 510515；南方医科大学中西医结合医院血液科，广东 广州 510000；深圳市前海蛇口自贸区医院血液科，广东 深圳 518067
  • 出版日期:2023-09-20 发布日期:2023-09-28

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

ZHANG Xiaomin, WU Zebin, LAN Huixuan, CHEN Shanshan, WU Jie, ZHU Lingling, XIAO Yang   

  1. 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
  • Online:2023-09-20 Published:2023-09-28

RichHTML

11

PDF

260

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cleavedPARP-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。

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

Abstract: 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.

Key words: deferoxamine; sublethal dose; X-ray irradiation; bone marrow hematopoiesis; vascular endothelial growth factor