Immunosuppression with a Combination of Triptolide and Cyclosporin A in Rat Vascularized Groin Flap Allotransplantation
Immunosuppression with a Combination of Triptolide and Cyclosporin A in Rat Vascularized Groin Flap Allotransplantation
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DOI：
10.1097/prs.0b013e31827c6daa
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发表时间：
2013-03-01
影响因子：
3.6
通讯作者：
Levin, L. Scott
中科院分区：
文献类型：
--
作者：
Liu, Fei;Luo, Xusong;Levin, L. Scott
背景：雷公藤内酯醇是一种从中药中提取的免疫抑制活性成分。在努力开发一种新的免疫抑制策略血管化复合同种异体移植，作者探讨了联合治疗与环孢素A和雷公藤甲素对大鼠腹股沟皮瓣allotransplants.Methods的生存的影响：腹股沟皮瓣移植从布朗挪威大鼠Fischer 344受体，然后用雷公藤甲素，环孢素A，或两者兼而有之。收集皮瓣活检标本，染色，并提交组织病理学评价。采用实时荧光定量PCR法检测脾脏中CCR5、CCR7、CCL19、CCL21和Foxp3的表达水平，流式细胞仪检测脾脏中CD4（+）CD25（+）调节性T细胞的百分率。接受雷公藤内酯醇和环孢素A的受者的平均移植物存活时间为57 +/-7.7天，而接受雷公藤内酯醇和环孢素A的受者的平均移植物存活时间为20.5 +/-7.7天。环孢菌素A单药组为2.3天，雷公藤内酯醇单药组为23.3 +/-3.6天，未治疗组为7.8 +/-0.8天。组织学检查也显示联合治疗的移植物中炎性细胞浸润减少。在联合治疗中CCR5、CCR7和CCL19的下调伴随着Foxp3表达的增加。流式细胞仪分析也显示，CD4（+）CD25（+）调节性T细胞的百分比在联合治疗组高于在single.Conclusions：雷公藤甲素和环孢素A的联合治疗显着延长移植物的生存，这意味着钙调神经磷酸酶相关的药物毒性可能会减轻和治疗费用降低。这种免疫抑制作用是通过抑制树突状细胞成熟和调节性T细胞扩增介导的。（Plast。重新配置131：343e，2013）。
Background: Triptolide is an immunosuppressive fraction purified from a Chinese medicinal plant. In an effort to develop a new immunosuppressive strategy for vascularized composite allotransplantation, the authors investigated the effects of combined treatment with cyclosporin A and triptolide on the survival of rat groin flap allotransplants.Methods: Groin flap transplantation was performed from Brown Norway rats to Fischer 344 recipients, which were then treated with triptolide, cyclosporin A, or both. Flap biopsy specimens were harvested, stained, and submitted to histopathologic evaluation. Levels of CCR5, CCR7, CCL19, CCL21, and Foxp3 in spleen were examined by real-time polymerase chain reaction, and the percentage of CD4(+)CD25(+) regulatory T cells was detected by flow cytometry.Results: The mean survival time for allografts in recipients receiving triptolide and cyclosporin A was 57 +/- 7.7 days compared with 20.5 +/- 2.3 days for cyclosporin A alone, 23.3 +/- 3.6 days for triptolide alone, and 7.8 +/- 0.8 days for no treatment. Histologic examination also showed that inflammatory cell infiltration was reduced in grafts with combination treatment. Down-regulation of CCR5, CCR7, and CCL19 in the combination treatment was accompanied by increased expression of Foxp3. Flow cytometric analysis also revealed that the percentage of CD4(+)CD25(+) regulatory T cells in the combination treatment was higher than in the monotherapy groups.Conclusions: Combination therapy with triptolide and cyclosporin A substantially prolonged allograft survival, which means calcineurin inhibitor-related drug-toxicity may be alleviated and treatment cost reduced. This immunosuppressive effect is mediated by inhibition of dendritic cells maturation and the expansion of regulatory T cells. (Plast. Reconstr. Surg. 131: 343e, 2013.)