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冬凌草甲素通过从外周血中清除T细胞来抑制移植排斥反应。

Oridonin suppresses transplant rejection by depleting T cells from the periphery.

作者信息

Guo Wenzhi, Zheng Peiguo, Zhang Jiakai, Ming Liang, Zhou Chuang, Zhang Shuijun

机构信息

Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China.

出版信息

Int Immunopharmacol. 2013 Dec;17(4):1148-54. doi: 10.1016/j.intimp.2013.10.023. Epub 2013 Nov 6.

Abstract

Oridonin is a natural compound purified from Rabdosia rubescens that has remarkable anti-inflammatory and antitumor activities. Although oridonin has been used in traditional Chinese medicine for many years to treat inflammatory diseases, the underlying mechanisms of these activities are not well understood. In this paper, we explored whether oridonin could be used in transplantation and the mechanisms of its immunosuppression. Oridonin efficacy in transplantation is manifested by prolonged graft survival and decreased graft infiltration. Oridonin induces T cell apoptosis in a concentration- and time-dependent manner. In vivo, oridonin depleted large numbers of T cells from the spleen and peripheral blood. Decreased T cell numbers resulted from apoptosis, which was accompanied by increased phagocyte numbers in the periphery. Reduction in the number of thymocytes was observed in mice treated for 8days, and CD4+CD8+ cells were more sensitive to apoptosis induced by oridonin. Additionally, successive treatment with oridonin for 16days resulted in a considerable reduction in the total number of spleen cells and spleen volume. Thus, T cell depletion may play an essential role in prolonged graft survival and immunosuppression induced by oridonin.

摘要

冬凌草甲素是从冬凌草中提纯出的一种天然化合物,具有显著的抗炎和抗肿瘤活性。尽管冬凌草甲素多年来一直被用于中药治疗炎症性疾病,但其这些活性的潜在机制尚未完全明确。在本文中,我们探究了冬凌草甲素是否可用于移植以及其免疫抑制机制。冬凌草甲素在移植中的疗效表现为延长移植物存活时间和减少移植物浸润。冬凌草甲素以浓度和时间依赖性方式诱导T细胞凋亡。在体内,冬凌草甲素使脾脏和外周血中的大量T细胞减少。T细胞数量减少是由凋亡导致的,同时外周吞噬细胞数量增加。在接受8天治疗的小鼠中观察到胸腺细胞数量减少,且CD4+CD8+细胞对冬凌草甲素诱导的凋亡更敏感。此外,连续16天用冬凌草甲素治疗导致脾细胞总数和脾脏体积显著减少。因此,T细胞耗竭可能在冬凌草甲素诱导的延长移植物存活和免疫抑制中起重要作用。

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