Epigallocatechin-3-gallate inhibits apoptosis and protects testicular seminiferous tubules from ischemia/reperfusion-induced inflammation

Epigallocatechin-3-gallate inhibits apoptosis and protects testicular seminiferous tubules from ischemia/reperfusion-induced inflammation
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DOI:
10.1016/j.bbrc.2012.03.013
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发表时间:
2012-04-06
影响因子:
3.1
通讯作者:
Al-Ajmi, Nada
Al-Ajmi, Nada
中科院分区:
生物学4区
文献类型:
--
作者:
Al-Maghrebi, May;Renno, Waleed M.;Al-Ajmi, Nada

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睾丸扭转(TT)是泌尿系统急症,可能导致未来不孕问题。TT的病理过程类似于缺血再灌注损伤(IRI)。本研究的目的是通过检测表没食子儿茶素-3-没食子酸酯(EGCG)在单侧IT大鼠模型中对炎症和凋亡介质表达的抑制作用,来评估其对逆转tt诱导的IRI损伤后果的作用。18只雄性Sprague-Dawley大鼠分为3组。第一组在全身麻醉下行左睾丸假手术。2组缺血1 h,生理盐水下再灌注4 h。第三组与第2组相似,但在缺血诱导后30 min腹腔注射EGCG (50 mg/kg)。采用ELISA法检测睾丸tnf - α、IL-6和IL-1 β水平,real-time PCR法检测iNOS、MCP-1、p53、Bax、Bcl-2和survivin mRNA表达,检测EGCG的体内保护作用。用H&E染色法和Johnsen评分法分别评价睾丸形态变化和精子发生损害。EGCG处理改善了同侧睾丸结构,显著抑制生殖细胞凋亡(GCA),显著降低睾丸细胞因子水平。此外,EGCG还能下调iNOS、MCP-1和促凋亡基因mRNA的表达,有利于细胞存活。我们首次证明,体内EGCG治疗可使扭曲的睾丸免于IRI诱导的炎症、GCA和精子发生损伤,从而为抑制tt诱导的IRI的炎症和凋亡后果提供了一种新的预防方法。(C) 2012爱思唯尔公司版权所有。
Testicular torsion (TT) is a urologic emergency that may result in future infertility problems. The pathologic process of TT is similar to an ischemia reperfusion injury (IRI). The purpose of this study was to evaluate the effect of epigallocatechin-3-gallate (EGCG) on reversing the damaging consequences of TT-induced IRI by examining its inhibitory effects on the expression of inflammatory and apoptosis mediators in a unilateral IT rat model. Eighteen male Sprague-Dawley rats were divided into 3 groups. Group 1 underwent a sham operation of the left testis under general anesthesia. Group 2 underwent ischemia for 1 h followed by 4 h reperfusion in the presence of saline. The third group was similar to group 2, however, EGCG (50 mg/kg) was injected i.p. 30 min after ischemia induction. The in vivo protective effect of EGCG was tested by measuring testicular levels of TNF-alpha, IL-6 and IL-1 beta by ELISA and mRNA expression of iNOS, MCP-1, p53, Bax, Bcl-2 and survivin by real-time PCR. Also, testicular morphological changes and damage to spermatogenesis were evaluated using H&E staining and Johnsen's scoring system, respectively. EGCG treatment improved testicular structures in the ipsilateral testis, markedly inhibited germ cell apoptosis (GCA) and significantly decreased testicular cytokine levels. In addition, EGCG was able to down regulate the mRNA expression of iNOS, MCP-1 and pro-apoptosis genes in favor of cell survival. For the first time we show that in vivo EGCG treatment rescued the torsed testes from IRI-induced inflammation, GCA and damage to spermatogenesis thus suggesting a new preventive approach to inhibiting the inflammatory and apoptotic consequences of TT-induced IRI. (C) 2012 Elsevier Inc. All rights reserved.