输注高表达IDO的供鼠树突状细胞对小鼠心脏移植排斥反应的抑制作用

Inhibitory effect of high expression of IDO from donor DCs on allograft rejection in mice heterotopic cardiac transplantation model

目的研究术前输注高表达吲哚胺2，3-双加氧酶（IDO）的供鼠树突状细胞（DC）对同种小鼠心脏移植后排斥反应的抑制作用。方法通过携带IDO基因的腺病毒转染供鼠DC获得IDO^＋DC建立小鼠同种异位心脏移植模型，术前给予受鼠不同干预，设立对照组、DC组和IDO组，观察各组移植心存活时间，术后7d获取移植心组织行病理学检查，采用聚合酶链反应检测IDOmRNA的表达水平，采用蛋白质印迹法检测DO蛋白的表达水平，应用流式细胞仪检测外周血T淋巴细胞的凋亡率。结果对照组、DC组和IDO组移植心的中位存活时间分别为7、7．5和17．5d，IDO组明显延长（P〈O．01）。与对照组和13（2组比较，IDO组移植心排斥反应病理分级明显降低（P〈0．01）。11）0组受鼠外周血CD3^＋T淋巴细胞的凋亡率高达（46．50±5．02）％，较其他两组明显升高（P〈0．01），且移植心组织1130表达水平亦明显增高（P〈O．01）。结论术前向受鼠输注转染IDO基因的供鼠DC可以诱导受鼠外周血T淋巴细胞的凋亡，对小鼠心脏移植排斥反应具有明显的抑制作用。

Objective To investigate the effect of high expression of functional IDO from donor DCs on transplantation rejection in mice heterotopic cardiac transplantation. Method Adenovirus vector containing IDO gene was used to infect donor （C57BL/6） DCs to obtain IDO^＋ DCs. Mouse heterotopic cardiac transplantation models were established （C57BL/6- BALB/c） and the following groups were set up： control group, DCs injection group and IDO^＋ DCs injection group. Survival time of the donor heart in all groups was observed. Meanwhile, donor hearts were harvested at 7 th day post-transplantation for different examinations, including pathological examination, mRNA expression of IDO by real-time PCR, and IDO protein expression by Western blotting. Peripheral blood of recipients was also harvested for T lymphocyte apoptosis rate examination by FACS. Result Cardiac allograft median survival time in control group, DCs injection group and IDO~ DCs injection group was 7,7. 5, and 17. 5 days respectively. IDO＋ DCs treatment significantly prolonged the survival time of donor hearts （P〈0. 01）. Pathological grading was significantly decreased （P〈0. 01）. The CD3^＋ T lymphocyte apoptosis rate in peripheral blood of recipients in IDO^＋ DCs injection group was （46. 50 ＋ 5.02） %, significantly higher than the other two groups （P〈0. 01）. Both IDO mRNA and protein expression showed significant increase （P 〈 0. 01 ）. Conclusion The pre-operative medication with IDO^＋ DCs injection to the recipients could induce T lymphocyte apoptosis and significantly suppress the rejection in mice heterotopic cardiac homotransplantation.