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多柔比星诱导的胸腺衰老。

Doxorubicin-induced thymus senescence.

机构信息

Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506, United States.

出版信息

J Proteome Res. 2010 Dec 3;9(12):6232-41. doi: 10.1021/pr100465m. Epub 2010 Nov 9.

DOI:10.1021/pr100465m
PMID:20945937
Abstract

Doxorubicin (DOX) is an anticancer drug used for the treatment of solid tumors. The ability of DOX to treat cancer is not specific to cancer cells; some of the cells that are normal may also become targets of DOX, thereby altering the normal cellular functions and eventual cell loss. DOX effects have been studied in detail in heart because of its ability to cause cardiomyopathy. The exact mechanism of DOX-induced cardiomyopathy is not completely understood. One of organs that can be affected by DOX is thymus. DOX treatment leads to degeneration of thymus; however, since thymus undergoes age-dependent degeneration, researchers have understudied the effect of DOX on thymus. In the present investigation, we studied the effects of DOX on thymus, an organ that is important for the T-cell maturation. DOX treatment led to loss of cortical cells, decrease lymphopoiesis and increased the number of Hassells corpuscles, a marker of thymus aging. Proteomics analysis led to identification of a number of thymic proteins whose expression are altered by in vivo DOX treatment. Taken together, these results are consistent with the notion that DOX-treatment leads to thymic senescence.

摘要

多柔比星(DOX)是一种用于治疗实体瘤的抗癌药物。DOX 治疗癌症的能力并非针对癌细胞,一些正常细胞也可能成为 DOX 的靶标,从而改变正常的细胞功能,最终导致细胞死亡。由于其导致心肌病的能力,DOX 的作用已在心脏中得到详细研究。DOX 诱导性心肌病的确切机制尚不完全清楚。一种可能受到 DOX 影响的器官是胸腺。DOX 治疗会导致胸腺退化;然而,由于胸腺随年龄而退化,研究人员对 DOX 对胸腺的影响研究不足。在本研究中,我们研究了 DOX 对胸腺的影响,胸腺是 T 细胞成熟的重要器官。DOX 治疗导致皮质细胞丢失,淋巴生成减少,Hassells 小体数量增加,这是胸腺衰老的标志。蛋白质组学分析鉴定出许多胸腺蛋白,其表达受体内 DOX 治疗的改变。总之,这些结果与 DOX 治疗导致胸腺衰老的观点一致。

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