中文摘要：

目的探讨吲哚胺2，3-双加氧酶（IDO）抑制小鼠异位心脏移植排斥反应的作用机制。方法通过携带IDO基因的腺病毒转染供体树突细胞（DC）而获得IDO＋DC，建立小鼠同种异位心脏移植模型，C57BL／6小鼠为供体，Balb／C小鼠为受体。分为空白对照组、DC注射组、色氨酸代谢产物（TC）注射组、IDO＋DC注射组和联合注射组（联合注射Tc及IDO＋DC），每组含供体、受体各12只；术前给予受体不同干预。观察移植心存活时间，术后7d获取移植心行组织病理学检查、real—timePCR检测IDOmRNA表达水平、Westernblot检测IDO蛋白表达水平，获取受体外周血行流式细胞学检测CD3＋T细胞凋亡率。采用单因素方差分析和Kaplan—Meier生存分析对IDO表达水平、CD3＋T细胞凋亡率及移植心存活时间进行统计学分析。结果空白对照组、DC注射组、TC注射组、IDO＋DC注射组及联合注射组移植心中位存活时间分别为7．0、7．5、11．0、17．5和24．0d。与空白对照组和DC注射组分别比较，TC注射组、IDO＋DC注射组及联合注射组移植心存活时间均延长（t=3．523～8．449，P〈0．01），移植心IDOmRNA和IDO蛋白表达水平均增高（t=5．974～16．176，P〈0．01），受体外周血CD3＋T细胞凋亡率均升高（t=6．324～38．120，P〈0．01）。与TC注射组和IDO＋DC注射组分别比较，联合注射组移植心中位存活时间延长（t=5．971和2．831，P〈0．05），移植心IDOmRNA和IDO蛋白表达水平增高（t=2．853～15．194，P〈0．01），受体外周血CD3＋T细胞凋亡率升高（t=26．069和7．643，P〈0．01）。结论术前向受体注射IDO＋供体DC及Tc均可抑制小鼠心脏移植排斥反应，而联合应用后的抑制作用更强，表明IDO通过“色氨酸饥饿”和“色氨酸代谢产物累积”两条途径同时发挥抗排斥作用。

英文摘要：

Objective To study the suppressive effect of indoleamine 2, 3-dioxygenase on transplantation rejection in mice heterotopic cardiac transplantation. Methods Adenovirus vector containing IDO gene was used to infect donor （C57BL/6） DC to obtain IDO＋ DC. Mouse heterotopic cardiac transplantation models were established （C57BL/6-BALB/c） and the following groups were set up, including the control group, DC injection group, TC injection group, IDO＋ DC injection group and co-injection group of IDO ＋ DC and TC, 12 donors and 12 recipients in each group. Survival time of the donor heart in every group was observed. Meanwhile, donor hearts were harvested 7 days post transplantation for different examinations, including pathological examination, mRNA expression of IDO through real-time PCR, IDO protein expression through Western blot. Peripheral blood of recipients was also harvested for CD3 ＋ T lymphocyte apoptosis rate examination through fluorescence-activated cell sorting. One-way ANOVA and Kaplan-Meier Survival Analysis were used for statistic analysis of IDO expression, CD3 ＋ T lymphocyte apoptosis rate and survival time of the donor heart respectively. Results Cadiac allograft median survival time of each group were 7.0, 7.5, 11.0, 17.5, 24. 0 days respectively. Compared with control and DC injection group, IDO ＋ DC, TC and co-injection group significantly prolonged the survival time of donor hearts（t = 3. 523-8.449, P 〈 0. 01 ）. Both IDO mRNA and protein expression showed significant increase （t =5. 974-16. 176 ,P 〈0. 01 ）. The CD3 ＋T lymphocyte apoptosis rate was also significantly increased （t = 6. 324-38. 120,P 〈 0.01 ）. Compared with IDO＋ DC or TC group alone, co-injection group significantly prolonged the survival time of the donor heart （ t = 5.971 and 2. 831, P 〈 0. 05 ）. Both IDO mRNA and protein expression showed significant increase （ t = 2. 853-15. 194, P 〈 0. 01 ）. Furthermore, the CD3 ＋ T lymphocyte apoptosis rate was significantly increased as well