减毒沙门氏菌介导的血小板第四因子活性片段的放射保护作用研究

目的:观察减毒沙门氏菌携带的血小板第四因子活性片段PF417 70 的放射保护作用。方法:通过口服途经喂饲小鼠携带PF4活性片段的减毒沙门氏菌,在第 2次喂饲后小鼠接受 70 0cGy全身照射,然后观察PIRES2 EGFP PF417 70 在小鼠体内的表达,并观察小鼠的造血恢复情况。结果:在小鼠的肝脏、脾脏、肾脏、小肠、外周血及骨髓均能检测到GFP的表达和转基因的整合。与对照组比较,实验组小鼠的生存期明显延长,照射后第 7d和 1 4d骨髓有核细胞数、骨髓培养的CFU GM和HPP CFC数量明显增加 (P <0 0 5 )。结论:首次应用减毒沙门氏菌SL32 61为载体来介导PF4活性片段的生物学作用,并证实通过口服途径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。

Radiation Protection of Platelet Factor 4 Fragment(PF417-70) Using Attenuated Salmonella as Oral Vectors for Gene Delivery

Objective: To study the radiation protection effect of PF4 17-70 on mice from total body irradiation using attenuated salmonella as gene delivery vectors. Methods: A live attenuated aroA-autotrophic mutant of salmonella typhimurium (SL3261) was used as carrier for eukaryotic vector PIRES2-EGFP/PF4 17-70 and was administered orally to BALB/C once at 3 day intervals. After the second oral administration the mice were injured by a total body irradiation (TBI) of 700 cGy using a 137 Cs source. GFP expression and gene integration were detected after administration. The survival rate, the number of bone marrow mononuclear cells and the forming ability of CFU-GM and HPP-CFC were measured. Results: GFP expression and gene integration could be found in liver, spleen, intestine, kidney, peripheral blood and bone marrow samples of treated mice. In comparison with control mice, the treated mice had a increased survival rate. Increased numbers of bone marrow mononuclear cells, CFU-GM and HPP -CFC were observed at 7?14 days after irradiation. Conclusion: These data demonstrate for the first time that an oral PF4 17-70 gene therapy using salmonella typhimurium as carrier protects mice from TBI damage and accelerates recovery of hematopoiesis in vivo. ;