FTY720预防小鼠同种异体胰岛移植的排斥反应  

Preventive Effect of FTY720 on Acute Rejection of Islet Allograft Transplantation in Mice

作　　者：刘龙山[1] 王长希[1] 张泳华 何晓顺[1] 尚文俊[1] 毕颖[1] 王东[1] 

机构地区：[1]中山大学附属第一医院器官移植科,广东广州510080 [2]杭州中美华东医药集团,浙江杭州310011

出　　处：《中山大学学报（医学科学版）》2006年第6期644-648,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：教育部回国留学基金资助项目(2003-14);广东省自然科学基金资助项目(2003B0202)

摘　　要：【目的】探讨FTY720在小鼠同种异体胰岛移植中的抗排斥作用及其机制。【方法】36只链脲霉素诱导的糖尿病小鼠(C57BL/6)随机分为3组,移植供体(Balb/c小鼠)胰岛后分别连续口服不同剂量的FTY720或双蒸水(对照组),FTY720剂量分别为0.5mg/(kg·d)(F0.5组)和1.0mg/(kg·d)(F1.0组)。术后连续测定血糖,行组织学检查对比淋巴细胞浸润程度,比较各组移植物中位存活时间(MST)。观察各组用药后不同时间外周血和肠系膜淋巴结(MLN)、腋窝淋巴结(ALN)中淋巴细胞数量的变化。【结果】F0.5组(84.5d)、F1.0组(>100d)MST明显长于对照组(10d)(P<0.01),F1.0组MST长于F0.5组(P<0.01)。用药组移植物中淋巴细胞浸润减轻并与剂量相关。F0.5组、F1.0组PBL变化趋势略有不同,分别在用药后8h、10h降至对照组的23.81%和12.59%(P<0.01),之后略有回升并趋于稳定。用药组连续口服FTY7205d后MLN、ALN中淋巴细胞数量明显高于对照组(P<0.05),连用14d后其淋巴细胞数量减少并低于对照组,尤以MLN明显。【结论】连续口服FTY720可有效延长小鼠同种异体胰岛移植物存活时间并呈一定的剂量相关性。FTY720可促进外周血淋巴细胞归巢至肠系膜和外周淋巴结,并诱导组织中淋巴细胞的凋亡,来减轻移植物中淋巴细胞浸润。[Objective] To investigate the anti-rejection effect of FTY 720 in islet allograft transplantation of mice and its mechanism.[Methods] 36 recipient mice （C57BL/6） were induced diabetes by streptozotocin （STZ） and then randomly divided into 3 groups. After islet allograft （Balb/c mice） transplantation, the 3 groups were orally administrated distilled water （control group） and different dose of FTY 720 [group F0.5：0.5 mg/（kg· d）, group F1.0：1.0 mg/（kg·d）]. Blood glucose was consecutively monitored, lymphocyte infiltration in islet allograft was observed by histopathology, and graft median survival time （MST） of each group was compared. The changes in lymphocyte counting of peripheral blood leukocytes （PBL）, mesenteric lymph node （MLN） and axillary lymph nodes （ALN） in each group were observed. [Results] The MST of group F0.5（84.5 d）and group F1.0（〉100 d）was significantly longer than that of control group （10 d）（P〈0.01）. The MST of group F1.0 was significantly longer than that of group F0.5（P〈 0.01 ）. Much less lymphocytes infdtration was found in FTY720 treated groups than in control group, which was dose related. Peripheral blood lymphocytes in group F0.5 and group F1.0 decreased to the lowest level at 8 h and 10 h after FTY720 administration respectively to 23.81% and 12.59% of that in control group, and then slightly came up to be stable. Lymphocytes in MLN and ALN in group F0.5 and group F1.0 were significantly higher than that in control group （P〈0.05）after 5 days of continuous FTY720 treatment, while decreased to be less than that in control group after 14 days of continuous FTY720 treatment, which was more apparent for lymphocytes in MLN. [ Conclusion ] Continuous administration of FTY720 can effectively prolong the survival time of islet allograft in mice, which is dose related. FTY720 can attenuate lymphocyte infdtration in graft probably by promoting peripheral blood lymphocytes homing into lymph nodes, as well as inducing apopt

关 键 词：同种异体胰岛移植 小鼠 免疫抑制剂 FTY720 淋巴细胞归巢 

分 类 号：R667.5[医药卫生—外科学]