酪氨酸磷酸化抑制剂AG 556对大鼠睾丸扭转所致缺血再灌注损伤的研究

Investigation of tyrphostin AG 556 for testicular torsion-induced ischemia reperfusion injury in rat.

作者信息

Karaguzel Ersagun, Sivrikaya Abdullah, Mentese Ahmet, Yulug Esin, Turkmen Suha, Kutlu Omer, Guler Yavuz, Us Diler, Turedi Suleyman, Alver Ahmet, Kazaz Ilke O

机构信息

Department of Urology, Karadeniz Technical University, Faculty of Medicine, Trabzon 61080, Turkey.

出版信息

J Pediatr Urol. 2014 Apr;10(2):223-9. doi: 10.1016/j.jpurol.2013.08.007. Epub 2013 Sep 11.

DOI:10.1016/j.jpurol.2013.08.007

PMID:24070787

Abstract

OBJECTIVE

To investigate the effects of tyrphostin AG 556, a tyrosine kinase inhibitor (TKI) in an experimental model of testicular ischemia-reperfusion (I/R) injury.

MATERIAL AND METHODS

Twenty-four adult male rats were randomly divided into four groups (n = 6): sham, torsion/detorsion (T/D), T/D + dimethylsulfoxide (DMSO) (vehicle group), and T/D + DMSO + tyrphostin AG 556. Testicular torsion was achieved by rotating the left testis 720° clockwise for 4 h. Thirty minutes before detorsion, 3 mg/kg tyrphostin AG 556 was injected transperitoneally in the AG 556 group and DMSO was injected transperitoneally in the DMSO group. After 2 h of reperfusion arterial blood samples were collected for biochemical analysis for malondialdehyde (MDA), ischemia modified albumin (IMA), SCUBE1 (signal peptide-CUB [complement C1r/C1s, Uegf, and Bmp1] and EGF [epidermal growth factor] like domain-containing protein 1), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) parameters, and ipsilateral orchiectomies were performed for histopathological examination based on the semi-quantitative Johnsen's mean testicular biopsy score (MTBS) in all groups.

RESULTS

Tyrphostin AG 556 exhibited a protective effect against I/R injury in testicular torsion. Of the biochemical parameters evaluated as a result of testicular I/R, IMA, MDA, and TOS levels were significantly elevated. There was no significant difference in terms of these biochemical parameters between the sham and AG 556 groups. Significant histopathological injury was determined by comparing the T/D and sham groups. According to histopathological injury scores, significant differences were determined between T/D and AG 556 groups and between AG 556 and sham groups. AG 556 had a superior improving effect on Johnsen's scores than DMSO.

CONCLUSIONS

Our results suggest that the use of tyrphostin AG 556 prior to testicular reperfusion has a protective effect against testicular I/R injury.

摘要

目的

在睾丸缺血再灌注（I/R）损伤实验模型中研究酪氨酸激酶抑制剂（TKI） tyrphostin AG 556的作用。

材料与方法

将24只成年雄性大鼠随机分为四组（n = 6）：假手术组、扭转/去扭转（T/D）组、T/D + 二甲基亚砜（DMSO）（溶剂组）和T/D + DMSO + tyrphostin AG 556组。通过将左侧睾丸顺时针旋转720°持续4小时来实现睾丸扭转。在去扭转前30分钟，AG 556组经腹腔注射3 mg/kg tyrphostin AG 556，DMSO组经腹腔注射DMSO。再灌注2小时后，采集动脉血样本进行生化分析，检测丙二醛（MDA）、缺血修饰白蛋白（IMA）、信号肽-CUB（补体C1r/C1s、Uegf和Bmp1）和EGF（表皮生长因子）样结构域包含蛋白1（SCUBE1）、总氧化剂状态（TOS）、总抗氧化剂状态（TAS）以及氧化应激指数（OSI）参数，并对所有组进行同侧睾丸切除术以基于半定量约翰森平均睾丸活检评分（MTBS）进行组织病理学检查。

结果

Tyrphostin AG 556对睾丸扭转中的I/R损伤表现出保护作用。作为睾丸I/R结果评估的生化参数中，IMA、MDA和TOS水平显著升高。假手术组和AG 556组在这些生化参数方面无显著差异。通过比较T/D组和假手术组确定了显著的组织病理学损伤。根据组织病理学损伤评分，T/D组和AG 556组之间以及AG 556组和假手术组之间存在显著差异。AG 556对约翰森评分的改善作用优于DMSO。