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用雌激素受体激动剂 ERβ 治疗可改善扭转诱导的大鼠氧化应激性睾丸损伤。

Treatment with estrogen receptor agonist ERβ improves torsion-induced oxidative testis injury in rats.

机构信息

Marmara University, School of Medicine, Department of Physiology, Istanbul, Turkey.

Marmara University, School of Medicine, Department of Histology & Embryology, Istanbul, Turkey.

出版信息

Life Sci. 2019 Apr 1;222:203-211. doi: 10.1016/j.lfs.2019.02.056. Epub 2019 Feb 27.

DOI:10.1016/j.lfs.2019.02.056
PMID:30825546
Abstract

AIMS

The purpose of the present study was to investigate the potential antioxidant, anti-apoptotic and sperm function-preserving effects of estrogen, estrogen receptor (ER)α and ERβ agonists in a rat model of testis torsion-detorsion (T/D).

MAIN METHODS

Under anesthesia, 6-8-week-old male Sprague-Dawley rats underwent sham-operation or testicular torsion by fixing left testis rotated at 720° for 2 h. After detorsion, rats were treated with ERα agonist (1 mg/kg/day, subcutaneously, sc) or ERβ agonist (1 mg/kg/day, sc) or estradiol (E, 1 mg/kg/day, in drinking water) or vehicle on the following two days. On the third day, testicular blood-flow was recorded and then left testes were extracted for molecular and histochemical analysis.

KEY FINDINGS

The findings showed that reduced testicular blood-flow following torsion was partially restored on the 3rd day of detorsion, while treatments with either of the ER agonists or E returned blood flow fully back to the control levels. When the testis-torsioned rats were given ERβ agonist during the detorsion period, tubular injury was lessened, sperm count and motility were increased, while the production of reactive oxygen metabolites and apoptosis in the testis tissues were totally suppressed. Although a down-regulated expression of androgen receptor (AR) along with a reduction in serum testosterone level was observed in the vehicle-treated T/D group, all three treatments up-regulated the expressions of AR and its mRNA, while ERα agonist and E suppressed the testosterone level.

SIGNIFICANCE

ERβ receptor activation during the post-ischemic period may be beneficial in protection against torsion-related oxidant testicular injury and infertility.

摘要

目的

本研究旨在探讨雌激素、雌激素受体(ER)α和 ERβ激动剂在睾丸扭转-复位(T/D)大鼠模型中潜在的抗氧化、抗凋亡和精子功能保护作用。

方法

在麻醉下,6-8 周龄雄性 Sprague-Dawley 大鼠接受假手术或睾丸扭转,将左侧睾丸固定旋转 720°2 小时。复位后,大鼠连续 2 天接受 ERα 激动剂(1mg/kg/天,皮下注射,sc)或 ERβ 激动剂(1mg/kg/天,sc)或雌二醇(E,1mg/kg/天,饮用水)或载体处理。第 3 天,记录睾丸血流,然后提取左侧睾丸进行分子和组织化学分析。

主要发现

扭转后睾丸血流减少在复位后第 3 天部分恢复,而用任一种 ER 激动剂或 E 处理可使血流完全恢复到对照水平。当在复位期间给予睾丸扭转大鼠 ERβ 激动剂时,管状损伤减轻,精子计数和活力增加,而睾丸组织中活性氧代谢物的产生和凋亡完全被抑制。尽管在载体处理的 T/D 组中观察到雄激素受体(AR)的表达下调以及血清睾酮水平降低,但三种处理方法均上调了 AR 的表达及其 mRNA,而 ERα 激动剂和 E 则抑制了睾酮水平。

意义

在缺血后期间激活 ERβ 受体可能有助于防止与扭转相关的氧化应激性睾丸损伤和不育。

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