口服携带人PF4基因的减毒沙门氏菌对大剂量化疗小鼠的促造血重建作用

Improved Hematopoiesis Reconstitution of Mice after Large Dose Chemotherapy by Using PF4 Gene Transfected Attenuated Salmonella typhmuriumas Orally

目的:探索口服携带人PF4基因的减毒沙门氏菌对大剂量化疗小鼠造血重建作用.方法:通过在大剂量化疗前/后喂服携带PIRES2-EGFP/PF4减毒沙门氏菌,检测化疗后小鼠的生存率,小鼠在不同时间外周血血常规、骨髓细胞数、骨髓中Sca-1和C-kit细胞含量、不同时间骨髓生成各系细胞的集落数等.结果:在大剂量化疗前、后均口服携带PIRES2-EGFP/PF4减毒沙门氏菌组小鼠生存率高于只在化疗前口服携带PIRES2-EGFP/PF4减毒沙门氏菌组;两组口服携带PIRES2-EGFP/PF4减毒沙门氏菌组小鼠存活率明显高于PBS对照组及携带空载体的减毒沙门氏菌组;口服携带PIRES2-EGFP/PF4减毒沙门氏菌组小鼠在化疗后第9～12天的外周血血小板数、骨髓细胞中Sca-1和C-kit阳性细胞含量明显比对照组高,第5天、9天、12天的骨髓细胞总数、骨髓细胞形成Mix集落数明显增加.结论:口服减毒沙门氏菌SL3261为载体的PF4基因可以保护小鼠免受损伤,并促进化疗损伤小鼠的造血恢复.

Aim:To study the effect of PF4 gene transfected attenuated Salmonella Typhmuriumas orally on the hematopoiesis reconstitution of mice after large dose of chemotherapy. Methods: Mice were treated with PIRES2-EGFP/ PF4 transfected attenuated Salmonella Typhmuriumas before and after large dose chemotherapy. Survival rate of mice after chemotherapy, the number of bone marrow cells,-Sca-1 and C-kit cells and colony forming units of different lineages in various time were detected. Results: PIRES2-EGFP/PF4 transfected attenuated Salmonella Typhmuriumas treated mice both before and after chemotherapy showed increased survival rate than those only treated with before chemotherapy. Both groups treated with PIRES2-EGFP/PF4 transfected attenuated Salmonella Typhmuriumas showed greater survival rate than the PBS group and non-carrier attenuated Salmonella Typhmuriumas group. Between the 9th and the 12th day after chemotherapy, in PIRES2-EGFP/PF4 transfected attenuated Salmonella Typhmuriumas group, platelet in peripheral blood and the percentage of Sca-1+ , C-kit+ cells were greater than in the control group. Bone marrow cells and their mix-CFU showed remarkable increase in the 5th ,9th and 12th day. Conclusions: Oral attenuated Salmonella Typhmuriumas SL3261 transfected with PF4 gene can protect mice from injury and promote the hematopoiesis reconstitution of chemotherapy injured mice.