阻断趋化因子受体途径对胰岛移植后急性排斥反应的影响  

Blocking the chemokine receptor pathway attenuates acute rejection after islet transplantation

作　　者：杨蕾[1] 刘永锋[1] 赵国华[1] 李铁民[1] 吴刚[1] 张佳林[1] 富大智[1] 

机构地区：[1]中国医科大学附属第一医院器官移植科,沈阳110001

出　　处：《中华器官移植杂志》2006年第7期396-398,共3页Chinese Journal of Organ Transplantation

摘　　要：目的探讨趋化因子拮抗剂Met-RANTES对大鼠同种异体胰岛移植后急性排斥反应的影响及其作用机制。方法实验分2个组进行，对照组仅行胰岛移植，实验组在胰岛移植后第1～7d腹腔内注射Met-RANTES 200μg／kg。术后监测大鼠的血糖变化及受者的存活情况，并观察移植胰岛的组织病理学变化；采用微量全血3H-胸腺嘧啶掺入法检测单个核细胞在刀豆蛋白A刺激下的增殖程度，流式细胞仪检测外周血CD4^＋细胞／CD8^＋细胞比值的变化及CCR5的表达。结果术后对照组和实验组血糖维持正常的时间分别为（3．8±4．5）d和（23．0±10．5）d，受者的存活时间分别为（11．4±4．2）d和（32．0±8．0）d，差异均有统计学意义（P〈0．05）；术后7d，对照组单个核细胞在刀豆蛋白A刺激下的增殖程度明显强于实验组（闪烁计数值分别为254．4次／min±116．3次／min和175．0次／min±98．2次／min），差异有统计学意义（P〈0．05）；两个组外周血CD4^＋细胞／CD8^＋细胞比值的差异无统计学意义，但对照组OER5的表达明显强于实验组，差异有统计学意义（P〈0．05）；术后第7d，对照组移植胰岛周围可见较多淋巴细胞浸润，胰岛细胞减少，而实验组移植胰岛周围淋巴细胞浸润少见，移植胰岛完整。结论Met-RANTES通过阻断趋化因子受体途径抑制单个核细胞的活性；移植术后应用Met-RANTES可明显抑制大鼠胰岛移植后排斥反应的发生，显著延长移植物及受者的存活时间。Objective To investigate the effects of chemokine antagonist, Met-RANTES, on the acute rejection of islet allograft in the rat model. Methods According to the different treatments, rats were divided into 2 group： control group, allogeneic islet transplant untreated; experiment group, allogeneic islet transplant treated with Met-RANTES （200μg/day, i. p） for 7 days post-operation. The survival time of rat of islet transplant and blood sugar were recorded, and the pathological changes of islet allograft were observed. Scintillation counter was used to count the count per min （cpm） of monocytes. Flow cytometry was used to detect the ratio of CD4^＋/CD8^＋ phenotypes and CCR5 expression of peripheral blood lymphocytes. Results The mean survival time of islet allograft in experiment group was 23. 0 ± 10. 5 days, obviously longer than in the control group （3. 8 ± 4. 5 days, P〈0. 05）. The mean survival time of recipients in the control and experiment groups was 11.4 ± 4. 2 days and 32. 0±8. 0 days, respectively, with the difference being significant. On the 7th day post-operation, proliferation degree of PBMC in the control group was higher than in the experiment group （254. 4 ±116.3 cpm vs 175. 0 ±98. 2 cpm）. Met-RANTES did not influence the ratio CD4^＋/CD8^＋ of lymphocytes. But the expression rate of CCR5 in experiment group was significantly lower than in control group （P〈0. 05）. On the 7th day postoperation, massive cellular infiltration around islet allografts were observed in the rats of control group. By contrast, less cellular infiltration was identified in the rats of experiment group. Conclusion Met-RANTES can block out chemokine receptor pathway and inhibit activation of monocytes. Thereby it can decrease acute rejection of islet allograft of rat and significantly prolong the survival time.

关 键 词：胰岛移植 RANTES 受体 CCR5 

分 类 号：R657.5[医药卫生—外科学]