常鹏宇,崔爽,姜新,曲超,蒋鑫萍,罗景华,曲雅勤,董丽华.脂肪干细胞修复辐射诱导的肠血管损伤研究[J].中华放射医学与防护杂志,2014,34(9):652-657
脂肪干细胞修复辐射诱导的肠血管损伤研究
Adipose-derived mesenchymal stem cell therapy for radiation-induced vascular injury in small intestine of rat
投稿时间:2014-03-27  
DOI:10.3760/cma.j.issn.0254-5098.2014.09.003
中文关键词:  脂肪干细胞  放射性肠损伤  血管  修复
英文关键词:Adipose-derived mesenchymal stem cells  Radiation-induced intestinal injury  Blood vessel  Repairation
基金项目:国家自然科学基金(81372929)
作者单位E-mail
常鹏宇 130021 长春, 吉林大学白求恩第一医院放疗科  
崔爽 130021 长春, 吉林大学白求恩第一医院放疗科  
姜新 130021 长春, 吉林大学白求恩第一医院放疗科  
曲超 130021 长春, 吉林大学白求恩第一医院放疗科  
蒋鑫萍 130021 长春, 吉林大学白求恩第一医院放疗科  
罗景华 130021 长春, 吉林大学白求恩第一医院放疗科  
曲雅勤 130021 长春, 吉林大学白求恩第一医院放疗科 quyaqin52@163.com 
董丽华 130021 长春, 吉林大学白求恩第一医院放疗科  
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中文摘要:
      目的 评价人源脂肪干细胞对辐射诱导的肠血管损伤的修复作用。方法 选用成年雄性SD大鼠,共34只,给予全腹部15 Gy X射线照射。造模后,取其中17只给予P6代人源脂肪干细胞腹腔注射治疗(Ad-MSC治疗组);另17只大鼠给予双磷酸盐缓冲液(PBS)腹腔注射治疗(PBS溶剂对照组)。照射后第10天,流式细胞分析绒毛内CD31阳性内皮细胞的数量,免疫荧光染色分析新生的血管内皮细胞,免疫组织化学染色分析血管结构的连续性;并提取受照小肠组织总RNA,实时荧光定量PCR检测受照组织内基质细胞起源因子-1(SDF-1)、血管内皮细胞生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)以及血管内皮细胞生长因子受体(Flk-1)的表达量。检测Ad-MSC治疗组的受损小肠内新生的内皮细胞来源。结果 与PBS溶剂对照组相比,Ad-MSC能够显著增加受损组织内CD31阳性内皮细胞数量(t=12.15,P<0.05),提高受损组织内的血管密度(20 d:t=10.33,P<0.05;30 d:t=32.85,P<0.05),上调血管生成基因VEGF、bFGF、Flk-1以及SDF-1的表达量(t=10.34、11.25、6.73、6.73,P<0.05)。维持受损部位小肠绒毛内的血管完整,并促进CD31阳性造血干/祖细胞向血管内皮细胞的分化,加速受损部位血管的新生。结论 人源脂肪干细胞通过发挥促血管新生的作用来修复辐射诱导的肠血管损伤。
英文摘要:
      Objective To assess the therapeutic effect of human adipose-derived mesenchymal stem cells on radiation-induced vascular injury in the small intestine of rat.Methods A total of 34 male Sprague-Dawley rats were enrolled in this study. To establish a model of radiation-induced intestinal injury, each rat was irradiated with 15 Gy in whole abdomen. 17 rats were randomly selected and infused intraperitoneally with passage 6 (P6) Ad-MSCs, and the other 17 rats that received PBS were set as control. 10 days post-irradiation, the number of CD31+ endothelial cells in the small intestine villus was measured by flow-cytometry, the expressions of CD31, CD105 and isolectin-B4 in the nave endothelial cells with detected by IHC-staining, and the vascular integrity was evaluated by measuring VE-Cadherin. The origination of nave endothelial cells within injured intestine was also analyzed. In addition, total mRNA were extracted from irradiated small intestine to assay the expressions of VEGF, bFGF, Flk-1 and SDF-1 using quantitative Real-time PCR.Results Compared to the control, the amount of CD31-postive endothelial cells within irradiated intestine was significantly increased after Ad-MSCs infusion (t=12.15, P<0.05). The microvascular density in the injured sites was also significantly increased by the infusion of Ad-MSCs (20 d: t=10.33, P<0.05;30 d: t=32.85, P<0.05). Moreover, the expressions of VEGF, bFGF, Flk-1 and SDF-1 were significantly up-regulated after delivery of Ad-MSCs (VEGF:t=10.34,bFGF:t=11.25,Flk-1:t=6.73, SDF-1:t=6.73, all P<0.05), which was beneficial in maintaining the integrity of intra-villus blood-vessels as well as promoting neovascularization in the injured sites.Conclusion Ad-MSCs had potentials in healing radiation-induced vascular injury in rat small intestine.
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