口服携带人血小板第四因子的减毒沙门氏菌对放射损伤的保护作用  

Protection from radiation injury through oral administration of PF4 gene carried by attenuated salmonella

作　　者：赵丽华[1] 刘斌[1] 余晓菲[1] 张磊[1] 韩忠朝[1] 

机构地区：[1]中国医学科学院中国协和医科大学血液学研究所,天津300020

出　　处：《中华放射医学与防护杂志》2005年第3期217-220,共4页Chinese Journal of Radiological Medicine and Protection

基　　金：国家杰出青年科学基金资助项目(39725014);国家自然科学基金资助项目(39780007);国家863资助项目(2001AA215311;2002AA223354);国家973资助项目(001CB5101)

摘　　要：目的以减毒沙门氏菌SL3261为载体研究通过口服途径血小板第四因子(plateletfactor4PF4)对小鼠放射损伤的保护作用。方法将携带PF4基因的真核表达载体pIRES2EGFP转化减毒沙门氏菌SL3261,通过口服途经1×108个3d个菌株的剂量饲服小鼠,在第3次饲服后12h小鼠接受700cGy剂量60Co全身照射。以绿色荧光蛋白(greenfluorescenceproteinGFP)、外周血象及流式的检测、骨髓集落培养、小鼠生存期的观察研究PF4对造血系统的保护作用。结果照射后SL3261PF4治疗小鼠的肝脏、脾脏、肾脏、小肠、外周血及骨髓分别检测到绿色荧光蛋白的表达。照射后第7和14天SL3261PF4组小鼠骨髓细胞总数(marrowmononuclearcellsMNC)、粒巨集落细胞形成细胞(granulocytemacrophagecolonyformingunitCFU-GM)和高增殖潜能集落形成细胞(highproliferatingpotentialcolonyformingcellsHPP-CFC)数量与对照组有明显差异(P<0.05),生存期明显延长。结论本研究首次证实以减毒沙门氏菌SL3261为载体,口服PF4基因治疗可以保护小鼠免受放射损伤,并促进放射损伤后小鼠的造血恢复。Objective To investigate the in vivo radiation protection effect of PF4 by oral administration of attenuated salmonella as the carrier in mice. Methods The eukaryotic vector pIRES2-EGFP-carried PF4 gene was transferred into an aroA-autotrophic mutant of salmonella typhimurium (SL3261) , which was administered orally to BALB/c mice at 1×10~8 PFu once every interval three days. At 12 hours after the third oral administration the mice were subjected to a total body irradiation (TBI) of 700 cGy by a ()^(60)Co source. The protective effect of SL3261/PF4 was determined by detection GFP(green fluorescence protein) expression in tissues, peripherial blood count, culture of bone marrow colony-forming cells and survival time of mice. Results (Expression of) GFP could be detected in the liver, spleen, intestine, kidney, peripheral blood and bone marrow. On days 7 and 14 after irradiation , Compared to controls , there were obvious differences in number of bone marrow mononuclear cells, CFU-GM (granulocyte-macrophage colony-forming unit) and HPP-CFC (high proliferating potential-colony-forming cells) of mice treated with SL3261/PF4 (P<0.05) as well as prolongation of the survival time . Conclusion These data demonstrate for the first time that PF4 protects mice from TBI injury and accelerates recovery of hematopoiesis by oral administration of attenuated salmonella carrying PF4 gene.;

关 键 词：减毒沙门氏菌 血小板第四因子 放射损伤 保护作用 高增殖潜能集落形成细胞 绿色荧光蛋白 protein cells factor 真核表达载体 ^60CO PF4 口服途径 载体研究 EGFP 全身照射 外周血象 集落培养 造血系统 观察研究 细胞总数 

分 类 号：R818[医药卫生—放射医学]