西罗莫司促进小鼠心脏移植模型中调节性T细胞的分化和增殖  

Sirolimus promotes differentiation and proliferation of regulatory T cells in mouse heart transplantation model

作　　者：谢江平[1] 张夕凉[1] 刘刚[1] 吴仕和[1] 王育红[1] 

机构地区：[1]海军总医院普外科,北京100048

出　　处：《器官移植》2015年第1期26-30,共5页Organ Transplantation

摘　　要：目的：探讨西罗莫司（SRL）对小鼠异位心脏移植模型的移植物存活时间以及脾脏中调节性T细胞（Treg）分化和增殖的影响。方法应用Cuff法建立雄性BALB／c→C57BL／6小鼠颈部异位心脏移植模型。术后随机分为3组各10只受体：对照组术后不予特殊药物治疗，SRL组术后1～14 d予SRL 10 mg／（kg·d）灌胃，环孢素（CsA）组术后1～14 d 予CsA 30 mg／（kg·d）灌胃。记录移植心脏存活时间，于移植心停搏或术后14 d取脾，分离单个核细胞，上流式细胞仪检测CD4＋CD25＋Treg占CD4＋T细胞比例（CD4＋CD25＋Treg％），采用逆转录-聚合酶链反应（RT-PCR）法半定量检测Foxp3信使核糖核酸（mRNA）表达水平。结果与对照组比较，CsA组和SRL组均明显延长小鼠移植心的生存时间（均为P＜0.01），而两者之间比较差异无统计学意义（P＞0.05）。与对照组比较，CsA组脾脏中CD4＋CD25＋Treg％明显降低，而SRL组则明显升高（均为P＜0.01），后两组比较差异有统计学意义（P＜0.01）。SRL组脾脏T细胞的Foxp3 mRNA表达明显高于对照组和CsA组，其中对照组亦明显高于CsA组（均为P＜0.01）。结论在小鼠心脏移植模型中，SRL明显延长移植物的存活期，促进CD4＋CD25＋Treg的增殖与生长，有利于免疫耐受的形成。Objective To investigate the impacts of sirolimus （SRL）on the survival time of graft and the differentiation and proliferation of regulatory T cell （Treg ） of spleen in mouse heterotopic heart transplantation model. Methods Male BALB /c → C57BL/6 mice cervical heterotopic heart transplantation model was established by Cuff method. The mice were divided into 3 groups randomly with 10 mice in each group. The control group received no treatment of special medicine after operation. Mice in SRL group were gavaged with SRL 10 mg/（kg·d）at 1-14 d after operation. Mice in ciclosporin （CsA）group were gavaged with CsA 30 mg/（kg·d） at 1-14 d after operation. The survival time of cardiac grafts were recorded. The spleen was procured after asystole of cardiac graft or 14 d after operation. Mononuclear cells were isolated and the proportion of CD4 ＋CD25 ＋Treg in CD4 ＋T cell （CD4 ＋CD25 ＋Treg%）were detected by flow cytometry and reverse transcription polymerase chain reaction （RT-PCR）was used to examine the expression of Foxp3 messenger ribonucleic acid （mRNA ） semi-quantitatively. Results Compared with the control group,the survival time of cardiac grafts prolonged significantly in SRL and CsA group （all in P 〈0.01 ）,but no significant difference was observed between SRL and CsA group （P〉0.05 ）. Compared with the control group,CD4 ＋CD25 ＋Treg% significantly decreased in the spleen of CsA group and significantly increased in SRL group （all in P〈0.01 ）. And significant difference was observed between SRL and CsA group （P〈0.01）. Expression of Foxp3 mRNA of T lymphocyte in the spleen of SRL group was significantly higher than those in control and CsA group （P〈0.01）. And expression of Foxp3 mRNA in control group was significantly higher than that in CsA group （P〈0.01 ）. Conclusions In mouse heart transplantation model,SRL can prolong the survival time of graft and promote the proliferation and growth of CD4 ＋CD25 ＋Treg to facilitate the establis

关 键 词：调节性T细胞 小鼠 心脏移植 西罗莫司 环孢素 

分 类 号：R617[医药卫生—外科学]