刘水冰,胡沛臻,侯颖,李旭波,田琼,石梅.重组人骨形成蛋白-2在造血损伤治疗中作用机制的探讨[J].中华放射医学与防护杂志,2009,29(2):139-142
重组人骨形成蛋白-2在造血损伤治疗中作用机制的探讨
Mechanism of recombinant human bone morphogenetic protein-2 in repairing hematopoietic injury in mice exposed to γ-rays
投稿时间:2008-04-16  
DOI:10.3760/cma.j.issn.0254-5098.2009.02.005
中文关键词:  骨形成蛋白  造血作用  辐射损伤  SRY基因  DNA探针
英文关键词:Bone morphogenetic protein  Hematopoiesis  Radiation injury  SRY gene  DNA probe
基金项目:国家自然科学基金(30470528)
作者单位E-mail
刘水冰 710032 西安, 第四军医大学药学系药理学教研室 tqiong@fmmu.edu.cn 
胡沛臻 710032 西安, 第四军医大学药学系病理学教研室  
侯颖 710032 西安, 第四军医大学药学系药理学教研室  
李旭波 710032 西安, 第四军医大学药学系药理学教研室  
田琼 710032 西安, 第四军医大学药学系药理学教研室  
石梅 西京医院  
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中文摘要:
      目的 探讨重组人骨形成蛋白-2(rhBMP-2)在治疗造血损伤中的作用机制,构建探针并通过原位杂交技术观察rhBMP-2治疗小鼠急性造血损伤的作用。方法 将22只BALB/c雌性小鼠随机分为照射组和骨形成蛋白治疗组。把正常雄性小鼠的骨髓细胞移植给接受8.5 Gy 60Coγ 射线照射的22只BALB/c雌性小鼠。14 d后,剩余存活的雌性小鼠左股骨再接受9 Gy的电子线照射。骨形成蛋白治疗组小鼠每天每只腹腔注射重组人骨形成蛋白-2 20 mg/kg,连续治疗6 d,照射对照组每天每只腹腔注射等量生理盐水。14 d后,处死小鼠并取股骨制成石蜡切片。用原位杂交技术检测雌性小鼠股骨中雄性供体小鼠的骨髓细胞。结果 原位杂交结果显示,照射组小鼠左股骨骨髓中的供体来源细胞数量明显比骨形成蛋白治疗组小鼠左股骨骨髓中多(T=155.0,P<0.05)。而照射组小鼠左股骨骨髓中供体来源细胞数量与2组小鼠右股骨骨髓中相比则无明显差异(T=92.0、78.5,P>0.05)。骨形成蛋白组小鼠左股骨骨髓中的供体来源细胞数量明显比两组小鼠右股骨骨髓中少(T=155.0、55.0,P<0.05)。结论 rhBMP-2促进了自身受损伤的骨髓细胞修复,故在骨形成蛋白组小鼠的左股骨骨髓中几乎检测不到供体雄性小鼠SRY基因的存在。推测rhBMP-2促进了自身骨髓间充质干细胞增殖或分化,并改善造血微环境,加快造血修复、重建的过程。
英文摘要:
      Objective To investigate the mechanism of recombinant human bone morphogenetic protein-2(rhBMP-2) in repairing hematopoietic injury in mice irradiated with γ-ray. To prepare SRY gene probe and study the effect of rhBMP-2 in repairing hematopoietic injury in mice by in situ hybridization.Methods Twenty-two BALB/c female mice were randomly divided into the irradiated group and BMP treated group, respectively. Bone marrow cells of normal male mice were transplanted into 22 female mice post-irradiation to 8.5 Gy of 60Coγ rays. The left femurs of the survived female mice were re-irradiated with 9 Gy 14 days later. Mice in BMP treated group were given rhBMP-2 20 mg/kg while those in control group were treated with 0.9% saline by intraperitoneal injection every day for 6 days. These mice were killed 14 days later and paraffin sections of femurs were made. The SRY gene was detected with in situ hybridization.Results There were more positive blots in the left femurs of the mice in irradiated group than those in BMP treated group(T=155.0,P<0.05). The number of positive blots between the left femurs of the mice in irradiated group and the right femurs of the mice in two groups was not significantly different(T=92.0,78.5,P>0.05). The number of positive blots in the left femurs of the mice in BMP treated group was significantly less than those in the right femurs of the mice in two groups(T=155.0,55.0,P<0.05).Conclusion No donor cell of male mice was detected in the left femurs of BMP treated group, suggesting that rhBMP-2 promoted the restoration of residuary bone marrow cells. Thus, rhBMP-2 promotes the proliferation or differentiation of residuary mesenchymal stem cells, improves hematopoietic microenvironment and accelerates the hematopoietic restoration.
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