重组胰岛素样生长因子-Ⅰ促进辐射损伤小鼠血小板水平的恢复  

Recombinant human insulin-like growth factor-Ⅰ promotes recovery of platelet in mice after radiation injury

作　　者：陈石磊[1] 陈芳[1] 许杨[1] 王崧[1] 王艾平[1] 粟永萍[1] 王军平[1] 

机构地区：[1]第三军医大学军事预防医学院全军复合伤研究所,创伤、烧伤与复合伤国家重点实验室,重庆400038

出　　处：《第三军医大学学报》2011年第22期2340-2344,共5页Journal of Third Military Medical University

基　　金：国家高技术研究发展计划(863计划,2007AA02Z152);国家自然科学基金(31076333)~~

摘　　要：目的观察重组人胰岛素样生长因子-Ⅰ(recombinant human insulin-like growth factor-Ⅰ,rhIGF-Ⅰ)对辐射损伤小鼠血小板水平的促恢复作用及其可能机制。方法健康BALB/c小鼠按完全随机法分为3组,其中2组小鼠接受全身一次性5 Gyγ射线辐照后,rhIGF-Ⅰ处理组连续7 d皮下注射rhIGF-Ⅰ,另一组(辐照对照组)及正常未辐照组皮下注射等量生理盐水。辐照后不同时相点尾静脉采血检测血常规,辐照后第14天病理切片观察骨髓组织变化;流式细胞仪分析未辐照小鼠Sca+-Ⅰ细胞经rhIGF-Ⅰ处理后CD41阳性率变化及rhIGF-Ⅰ对辐照所致巨核祖细胞凋亡的影响。结果rhIGF-Ⅰ处理组小鼠在辐照后11～17 d期间血小板数量显著高于辐照对照组(P<0.01)。体外分离培养的rhIGF-Ⅰ处理组Sca+-Ⅰ细胞CD41阳性率及c-kit+细胞阳性率分别为(24.10±2.43)%、(47.84±6.02)%,显著高于空白对照组(15.40±3.25)%和辐照对照组(24.68±5.83)%;巨核祖细胞辐照后给予rhIGF-Ⅰ处理,其凋亡率为(38.76±2.85)%,也明显低于辐照对照组的(50.58±4.32)%,上述结果差异均具有统计学意义(P<0.05)。此外,病理切片显示,rhIGF-Ⅰ处理组小鼠骨髓有核细胞和巨核细胞数目也显著高于辐照对照组。结论 rhIGF-Ⅰ可能通过促进造血干细胞向巨核细胞分化并抑制巨核祖细胞凋亡,从而保护辐照所致的巨核细胞损伤并促进血小板水平的恢复。Objective To investigate the effect of recombinant human insulin-like growth factor-Ⅰ（rhIGF-Ⅰ） on the thrombopoiesis of irradiated mice and its possible mechanism.Methods BALB/c mice were randomly divided into three groups,two of them were subjected to total body irradiation at a dose of 5 Gy,while the IGF-Ⅰ treated group were injected subcutaneously with rhIGF-Ⅰ for 7 d,the irradiated and normal group were given the same volume saline.Blood samples were tested at different time points with blood corpuscle analyzer,the changes in bone marrow at the 14th day was examined with pathological sections;the effect of rhIGF-Ⅰ on murine Sca＋-Ⅰ cells differentiating into megakaryocytes and radiation-induced apoptosis of megakaryocytes was analyzed with flow cytometry.Results The platelet counts in rhIGF-Ⅰ treated group at the 11-17th day after irradiation injury were significantly higher than in saline control group,moreover,the frequency of CD41 in isolated Sca＋-Ⅰcells and c-kit＋ cells were（24.10±2.43）% and（47.84±6.02）%,respectively,which were significantly higher than those in control group which were（15.40±3.25）% and（24.68±5.83）%.Furthermore,the apoptosis frequency of megakaryocyte with rhIGF-Ⅰ treatment was（38.76±2.85）%,which was also significantly lower than in the control group [（50.58±4.32）%] after irradiation exposure（P0.05）.In addition,the number of bone marrow nucleated cells was significantly higher than that in the saline control group.Conclusion rhIGF-Ⅰ may promote the differentiation of hematopoietic stem cells to megakaryocytes and inhibit apoptosis of megakaryocytes,which plays its promoting-recovery effect on radiation-induced megakaryocytes damage and decrease of platelet counts.

关 键 词：胰岛素样生长因子-Ⅰ 辐照损伤 血小板 

分 类 号：R818.74[医药卫生—放射医学] R331.22[医药卫生—临床医学]