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替米沙坦和氯沙坦对受辐照睾丸的影响。

Effects of telmisartan and losartan on irradiated testes.

作者信息

da Silva Mansano Naira, Jorge Isabela Fernandes, Chies Agnaldo Bruno, Viani Gustavo Arruda, Spadella Maria Angélica

机构信息

Marília Medical School, Marília, São Paulo, Brazil.

Psychiatric Resident, Institute for Medical Assistance for State-Level Government Employees (IAMSPE), São Paulo, São Paulo, Brazil.

出版信息

Life Sci. 2018 Feb 1;194:157-167. doi: 10.1016/j.lfs.2017.12.031. Epub 2017 Dec 27.

Abstract

AIMS

To analyze the effects of radiation on the reproductive tissue of male Wistar rats and to evaluate whether treatment with the Ang II AT1 receptor antagonists telmisartan and losartan mitigate the dysfunctions resulting from this exposure.

MAIN METHODS

Rats were randomly divided into groups: Control, Irradiated, Telmisartan, Losartan, Irradiated+Telmisartan, and Irradiated+Losartan. Single dose of 5Gy was administered directly into the scrotum, followed by treatment with telmisartan (12mg/kg/day) or losartan (34mg/kg/two times/day) for 60days. Testicular function parameters were evaluated from spermatozoa of the vas deferens. Testes were processed for histopathological and morphometric-stereological analysis. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was evaluated.

KEY FINDINGS

Radiation significantly reduced sperm motility, concentration, vitality, and increased the number of abnormal spermatozoa. Telmisartan and losartan did not significantly prevent these radiation-induced disorders. Seminiferous tubules were atrophied in both untreated and treated irradiated testes, and exhibited vacuoles, increased interstitial tissue and high number of blood vessels. However, several seminiferous tubules in recuperation were founded among damaged tubules in the testes of treated animals. The PCNA immunohistochemistry confirmed these outcomes. PCNA-positive cells were detected in dividing spermatogonia and spermatocytes from irradiated telmisartan and losartan treated rats whereas in the only-irradiated group, PCNA staining was observed in the nuclei of only the surviving spermatogonia.

SIGNIFICANCE

Under these experimental conditions, the testicular function parameters showed that radiation produced marked damage that was not reversed by treatments. However, gonadal restructuring and recovery of spermatogenesis in treated animals may to reflect attenuation of radiation-induced damages and potential start of recovery.

摘要

目的

分析辐射对雄性Wistar大鼠生殖组织的影响,并评估使用血管紧张素II 1型受体拮抗剂替米沙坦和氯沙坦进行治疗是否能减轻这种辐射暴露导致的功能障碍。

主要方法

将大鼠随机分为几组:对照组、辐射组、替米沙坦组、氯沙坦组、辐射 + 替米沙坦组和辐射 + 氯沙坦组。对阴囊直接给予单次5Gy剂量的辐射,随后用替米沙坦(12mg/kg/天)或氯沙坦(34mg/kg/每天两次)治疗60天。从输精管的精子中评估睾丸功能参数。对睾丸进行组织病理学和形态计量 - 体视学分析。评估增殖细胞核抗原(PCNA)免疫组化情况。

主要发现

辐射显著降低了精子活力、浓度、存活率,并增加了异常精子的数量。替米沙坦和氯沙坦并未显著预防这些辐射诱导的紊乱。在未治疗和接受治疗的辐射睾丸中,生精小管均萎缩,并出现空泡、间质组织增加和血管数量增多的情况。然而,在接受治疗动物的睾丸中,受损小管之间发现了一些正在恢复的生精小管。PCNA免疫组化证实了这些结果。在接受辐射、替米沙坦和氯沙坦治疗的大鼠的分裂精原细胞和精母细胞中检测到PCNA阳性细胞,而在仅接受辐射的组中,仅在存活的精原细胞核中观察到PCNA染色。

意义

在这些实验条件下,睾丸功能参数表明辐射造成了明显损伤,治疗并未使其逆转。然而,接受治疗动物的性腺重构和精子发生的恢复可能反映了辐射诱导损伤的减轻以及潜在的恢复开始。

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