中华放射医学与防护杂志

赵丽华,刘斌,余晓菲,等.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[J].中华放射医学与防护杂志,2005,25(3):217-220.ZHAO Li-hua,LIU Bin,YU Xiao-fei,et al.Protection from radiation injury through oral administration of PF4 gene carried by attenuated salmonella[J].Chin J Radiol Med Prot,2005,25(3):217-220

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

投稿时间：2004-04-29

DOI：

中文关键词: 沙门氏菌血小板第四因子放射损伤口服

英文关键词:Attenuated salmonella Platelet factor 4 Radiation injury Oral administration

基金项目: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)

作者	单位	E-mail
赵丽华	300020 天津, 中国医学科学院中国协和医科大学血液学研究所	tihzchan@public.tpt.tj.cn
刘斌	300020 天津, 中国医学科学院中国协和医科大学血液学研究所
余晓菲	300020 天津, 中国医学科学院中国协和医科大学血液学研究所
张磊	300020 天津, 中国医学科学院中国协和医科大学血液学研究所
韩忠朝	300020 天津, 中国医学科学院中国协和医科大学血液学研究所

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中文摘要:

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(platelet factor 4 PF4)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pIRES2-EGFP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(green fluorescence protein GFP)、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(marrow mononuclear cells MNC)、粒巨集落细胞形成细胞(granulocyte-macrophage-colony-forming-unit CFU-GM)和高增殖潜能集落形成细胞(high-proliferating-potential-colony forming cells HPP-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。

英文摘要:

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 1×10⁸ 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 ⁶⁰Co 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.

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