HSV-sr39TK-GCV／ACV系统抑制小鼠异基因骨髓移植后移植物抗宿主病  

Prevention and treatment of GVHD mediated by herpes simplex virus-semi random 39 thymidine kinaseganciclovir/acyclovir after murine allo-bone marrow transplantation

作　　者：朱锋[1] 徐开林[1] 杜冰[1] 潘秀英[1] 曾令宇[1] 鹿群先[1] 

机构地区：[1]徐州医学院附属医院血液科,江苏221002

出　　处：《中华器官移植杂志》2008年第9期531-535,共5页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金（30170389）;江苏省“135”医学重点人才项目（RC2002080）

摘　　要：目的研究突变型单纯疱疹病毒胸苷激酶-更昔洛韦／阿昔洛韦（HSV-sr39TK-GCV／ACV）系统对小鼠异基因骨髓移植后移植物抗宿主病（GVHD）的影响。方法采用改良的磷酸钙沉淀法．以携带HSV-sr39TK基因的慢病毒感染C57BL／6小鼠的脾淋巴细胞，制得sr39TK^＋T淋巴细胞。以C57BL／6小鼠为供者，Balb／c小鼠为受者进行骨髓移植，受者移植前接受^60Coγ射线照射。实验分6组进行：（1）GCV组共30只小鼠．均于骨髓移植的同时输注sr39TK^＋T淋巴细胞．其中10只于骨髓移植当天至第6天腹腔注射GCV0．5mg／d，10只于骨髓移植后第7～13天腹腔注射GCV0．5mg／d，10只于骨髓移植后第12～18天腹腔注射GCV0．5mg／d；（2）ACV组共30只小鼠，骨髓移植与sr39TK^＋T淋巴细胞输注同GCV组．其中10只于骨髓移植当天至第6天腹腔注射ACV0．5mg／d，10只于骨髓移植后第7～13天腹腔注射ACV0．5mg／d，10只于骨髓移植后第12～18天腹腔注射ACV0．5mg／d；（3）移植对照组仅行骨髓移植；（4）脾细胞对照组行骨髓移植和睥淋巴细胞输注；（5）GCV对照组在脾细胞对照组的基础上于骨髓移植后第7～13天腹腔注射GCV0．5mg／d。（6）sr39TK对照组行骨髓移植和sr39TK^＋T淋巴细胞输注。观察各组受者的存活时间、GVHD的发生情况及程度。结果GCV对照组、sr39TK对照组、脾细胞对照组和移植对照组小鼠均于骨髓移植后19d内死亡。GCV组移植当天用药者、第7天用药者和第12天用药者的存活时间分别为（36．70±5．20）d、（40．30±4．69）d和（27．10±4．85）d。ACV组移植当天用药者、第7天用药者和第12天用药者的存活时间分别为（36．50±5．26）d、（46．20±3．61）d和（3（1．90±5．21）d。GCV组和ACV组受者的存活时间均长于4个对照组（P〈0．01）。GCV组和ACV组中第7天用药者的存活时间和50d存活率优于其它各时间用药者，差异有�Objective To study whether herpes simplex virus semi random 39 thymidine kinaseganciclovir/acyclovir （HSV-sr39TK GCV/ACV） could prevent and treat graft-versus host disease （GVHD） after murine allo-bone marrow transplantation （allo-BMT）. Methods Donor splenic lymphocytes were infected by lentiviral vectors carrying HSV-sr39TK. With donor bone marrow cells, they were both transplanted into recipient mice irradiated by ^60Co γ ray. C57BL/6 mice were used as the donor mice. Balb/c mice were used as the recipient mice. GCV/ACV was administered for 7 days by intraperitoneal injection after transplantation. The recipient mice were divided into 6 groups.. （1） GCV groups. These mice were transplanted with bone marrow cells and sr39TK^＋ T lymphocytes.Ten mice were administered with GCV 0. 5 mg/d between 0 day and 6 day after transplantation. Ten were administered with GCV 0. 5 mg/d between 7 day and 13 day after transplantation. And the others were administered with GCV between 12 day and 18 day after transplantation; （2） ACV groups. These mice were transplanted with bone marrow cells and sr39TK^＋ T lymphocytes. Ten mice were administered with ACV 0. 5 mg/d between 0 day and 6 day after transplantation. Ten were administered with ACV 0. 5 mg/d between 7 day and 13 day after transplantation. And the others were administered with ACV between 12 day and 18 day after transplantation; （3） Transplantation control group. These mice were only transplanted with bone marrow cells; （4） Splenic lymphocytes control group. These mice were transplanted bone marrow cells and splenic lymphocytes; （5） GCV control group. These mice were transplanted with bone marrow cells and splenic lymphocytes, and administered with GCV （）. S mg/d between 7 day and 13 day after transplantation; （6） sr39TK control group. These mice were transplanted with bone marrow cells and sr39TK^＋ T lymphocytes. The survival time, incidence of GVHD, T lymphocytes immunity reconstruction and the ratio of allogeneic chimeras

关 键 词：基因 转基因 自杀 移植物抗宿主病 骨髓移植 单纯疱疹病毒属 胸苷激酶 

分 类 号：R457.7[医药卫生—治疗学]