Gu Chuan, Liu Fei, Luo Xusong, Zhou Xianyu, Yang Jun, Levin L Scott
Shanghai, People's Republic of China; and Philadelphia, Pa.
From the Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine; and the Department of Orthopedic Surgery, Hospital of the University of Pennsylvania.
Plast Reconstr Surg. 2016 Dec;138(6):1243-1253. doi: 10.1097/PRS.0000000000002770.
Induction of tolerance and minimizing the toxicity of immunosuppression are two fundamental goals in vascularized composite allotransplantation. Accumulating data indicate that triptolide is an agent that may have the capacity to suppress inflammation and immunologic rejection.
A heterotopic hindlimb allotransplantation model from Brown Norway to Lewis rats was established and treated with different doses of tacrolimus combined with or without triptolide. Mean survival time of the transplants was monitored, and histopathologic examination of the skin was performed. The level of inflammatory cytokine interleukin-1β, interleukin-6, and tumor necrosis factor-á in peripheral blood was assayed. The percentage of T lymphocytes and its subsets was measured using flow cytometry. The level of recipient peripheral chimerism and the apoptosis of donor bone marrow cells were evaluated. The apoptotic related genes bcl-2 and Bax were detected by real-time polymerase chain reaction.
The authors' results showed that triptolide not only reduces the dose of tacrolimus required for immunosuppression, but also decreased drug side effects in terms of weight gain and diarrhea. Triptolide had an obvious effect on proinflammatory cytokine expression and T-lymphocyte proliferation in the peripheral blood. Interestingly, triptolide could increase the mixed chimerism level of recipients, possibly by inhibiting the apoptosis of transplanted bone marrow cells by means of regulation of the apoptotic genes bcl-2 and Bax.
Triptolide reduces the dose of tacrolimus required for immunosuppression by attenuating inflammation and by T-cell suppression. Furthermore, triptolide increases the chimerism level, which might contribute to acceptance of the allografts.
诱导免疫耐受并将免疫抑制的毒性降至最低是血管化复合组织异体移植的两个基本目标。越来越多的数据表明，雷公藤内酯醇是一种可能具有抑制炎症和免疫排斥能力的药物。
建立从棕色挪威大鼠到刘易斯大鼠的异位后肢异体移植模型，并用不同剂量的他克莫司联合或不联合雷公藤内酯醇进行治疗。监测移植物的平均存活时间，并对皮肤进行组织病理学检查。检测外周血中炎性细胞因子白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α的水平。使用流式细胞术测量T淋巴细胞及其亚群的百分比。评估受体外周嵌合水平和供体骨髓细胞的凋亡情况。通过实时聚合酶链反应检测凋亡相关基因bcl-2和Bax。
作者的结果表明，雷公藤内酯醇不仅降低了免疫抑制所需的他克莫司剂量，而且在体重增加和腹泻方面减少了药物副作用。雷公藤内酯醇对外周血中促炎细胞因子表达和T淋巴细胞增殖有明显影响。有趣的是，雷公藤内酯醇可能通过调节凋亡基因bcl-2和Bax抑制移植骨髓细胞的凋亡，从而提高受体的混合嵌合水平。
雷公藤内酯醇通过减轻炎症和抑制T细胞来降低免疫抑制所需的他克莫司剂量。此外，雷公藤内酯醇提高了嵌合水平，这可能有助于同种异体移植物的接受。
