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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

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【作者】 闫凤英卢士红许子亮刘斌赵丽华梁琳慧宋忻杨发金韩忠朝

【Author】 YAN Feng-ying LU Shi-hong XU Zi-ling LIU Bin ZHAO Li-hua LIANG Lin-hui SONG XinYANG Fa-jin HAN Zhong-chao(State key Laboratory of Experimental Hematology,Institute of Hematology,CAMS & PUMC Tianjin 300020,China)

【机构】 中国医学科学院中国协和医科大学血液学研究所实验血液学国家重点实验室中国医学科学院中国协和医科大学血液学研究所实验血液学国家重点实验室 天津 300020天津 300020天津 300020

【摘要】 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。

【Abstract】 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.

【基金】 国家"863"计划资助项目(2003AA205060)国际合作重点项目(2002AA217041)国家"973"计划资助项目(001CB5101)CMB基金资助项目(#01-749)
  • 【文献出处】 中国生物工程杂志 ,Progress In Biotechnology , 编辑部邮箱 ,2005年02期
  • 【分类号】R965
  • 【被引频次】1
  • 【下载频次】78
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