Department of Biochemistry, Faculty of Medicine, Kuwait University, PO Box: 24923, Safat 13110, Kuwait.
Biochem Biophys Res Commun. 2012 Apr 6;420(2):434-9. doi: 10.1016/j.bbrc.2012.03.013. Epub 2012 Mar 9.
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 TT 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 1h followed by 4h 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-α, IL-6 and IL-1β 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.
睾丸扭转(TT)是一种泌尿科急症,可能导致未来的生育问题。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 EGCG 对单侧 TT 大鼠模型中炎症和凋亡介质表达的抑制作用,评估其逆转 TT 诱导的 IRI 破坏性后果的效果。
将 18 只雄性 Sprague-Dawley 大鼠分为 3 组。第 1 组在全身麻醉下接受左侧睾丸假手术。第 2 组在存在盐水的情况下进行 1 小时缺血,然后再进行 4 小时再灌注。第 3 组与第 2 组相似,然而,在缺血诱导后 30 分钟,EGCG(50mg/kg)通过 i.p. 注射。通过 ELISA 测量睾丸 TNF-α、IL-6 和 IL-1β 的水平以及实时 PCR 测量 iNOS、MCP-1、p53、Bax、Bcl-2 和 survivin 的 mRNA 表达来测试 EGCG 的体内保护作用。此外,通过 H&E 染色和 Johnsen 评分系统分别评估睾丸形态变化和生精细胞损伤。
EGCG 治疗改善了同侧睾丸的结构,显著抑制了生精细胞凋亡(GCA),并显著降低了睾丸细胞因子水平。此外,EGCG 能够下调 iNOS、MCP-1 和促凋亡基因的 mRNA 表达,有利于细胞存活。我们首次表明,体内 EGCG 治疗可使扭转的睾丸免受 IRI 引起的炎症、GCA 和生精损伤的影响,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。