Reversal of age-related thymic involution by an LHRH agonist in miniature swine
Reversal of age-related thymic involution by an LHRH agonist in miniature swine
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DOI：
10.1016/j.trim.2010.08.001
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发表时间：
2010-10-01
影响因子：
1.5
通讯作者：
Yamada, Kazuhiko
中科院分区：
文献类型：
--
作者：
Hirakata, Atsushi;Okumi, Masayoshi;Yamada, Kazuhiko
研究背景和目的：我们以前已经证明了需要幼年胸腺的存在下，诱导移植耐受性肾同种异体移植的短期钙调磷酸酶抑制小型猪。我们还发现，当将带血管的胸腺叶移植到幼年猪受体中时，老化的退化胸腺可以恢复活力。本研究旨在阐明促进老年胸腺功能恢复的外在因素。特别地，我们测试了促黄体生成素释放激素（LHRH）对性类固醇阻断的影响。材料和方法：30只幼稚动物（25只雄性和5只雌性）用于测量血清睾酮水平。使用3只成年雄性猪（年龄为22、22和29月龄）测试Lupron（LHRH类似物）注射45 mg（每70-80 kg体重）作为3个月储药对睾酮水平和胸腺再生的影响。胸腺年轻化进行了评估，组织学，流式细胞仪分析，形态分析和TREC assessment.Results：激素的变化引起Lupron和导致宏观和组织再生的老年动物的胸腺在2个月内，证明恢复少年胸腺结构和增加细胞。两个动物的TREC进行了评估，都表现出增加的水平，在周边以下Lupron treatment.Conclusion：治疗老年动物Lupron导致胸腺rejuventaion在成年小型猪。这一结果可以扩大胸腺依赖性耐受诱导方案对成年受体的适用性。(C)2010爱思唯尔有限公司版权所有。
Background and aims of study: We have previously demonstrated a requirement for the presence of a juvenile thymus for the induction of transplantation tolerance to renal allografts by a short-course of calcineurin inhibition in miniature swine. We have also shown that aged, involuted thymi can be rejuvenated when transplanted as vascularized thymic lobes into juvenile swine recipients. The present studies were aimed at elucidating the extrinsic factors facilitating this restoration of function in the aged thymus. In particular, we tested the impact of sex steroid blockade by Luteinizing Hormone-Releasing Hormone (LHRH).Materials and methods: 30 naive animals (25 males and 5 females) were used for measurement of serum testosterone levels. 3 mature male pigs (aged at 22, 22 and 29 months old) were used to test the effects of Lupron (LHRH analog) injection at 45 mg (per 70-80 kg body weight) as a 3-month depot on testosterone levels and thymic rejuvenation. Thymic rejuvenation was assessed by histology, flow cytometric analysis, morphometric analysis and TREC assays.Results: Hormonal alterations were induced by Lupron and resulted in macroscopic and histologic regeneration of the thymus of aged animals within 2 months, as evidenced by restoration of juvenile thymus architecture and increased cellularity. Two animals that were evaluated for TREC both showed increased levels in the periphery following Lupron treatment.Conclusion: Treatment of aged animals with Lupron leads to thymic rejuventaion in adult miniature swine. This result could expand the applicability of thymus-dependent tolerance-inducing regimens to adult recipients. (C) 2010 Elsevier B.V. All rights reserved.