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舒马曲坦对大鼠扭转/复位后同侧和对侧睾丸缺血/再灌注损伤的保护作用。

Protective effects of sumatriptan on ischaemia/reperfusion injury following torsion/detorsion in ipsilateral and contralateral testes of rat.

机构信息

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Andrologia. 2019 Oct;51(9):e13358. doi: 10.1111/and.13358. Epub 2019 Jul 9.

Abstract

This study was planned to evaluate the effects of sumatriptan, 5-HT1B/1D receptors agonist, on ischaemia/reperfusion injury in bilateral testes after unilateral testicular torsion/detorsion in rats. Male Wistar rats (n = 42) were allocated into a sham-operated group, a control group and treatment groups which were injected sumatriptan (0.1, 0.3 and 1 mg/kg), GR-127935 (0.01 mg/kg)-5-HT1B/1D receptors antagonist-and sumatriptan (0.1 mg/kg) + GR-127935 (0.01 mg/kg). Torsion was induced for 1 hr by rotating right testis 720 in the clockwise direction, and after 7 days of detorsion, bilateral orchiectomy was conducted. While the level of TNF-α rose in testicular tissue after inducing torsion/detorsion, sumatriptan injection notably lowered TNF-α level in ipsilateral (torted) and contralateral (nontorted) testes (p < 0.001). Moreover, after inducing testicular torsion/detorsion, SOD activity was decreased, whereas administration of sumatriptan significantly increased SOD activity in bilateral testes (p < 0.001). After induction of torsion/detorsion, macroscopic and histological analyses also showed severe damages which were improved by sumatriptan injection. Interestingly, co-administration of sumatriptan with GR-127935 reversed the beneficial impacts of sumatriptan on macroscopic appearance, microscopic pattern and biochemical markers. It is concluded that sumatriptan presumably via stimulation of 5-HT receptors decreased inflammation, oxidative stress and deteriorations induced by ischaemia/reperfusion injury following testicular torsion/detorsion.

摘要

本研究旨在评估 5-HT1B/1D 受体激动剂舒马曲坦对单侧睾丸扭转/复位后双侧睾丸缺血再灌注损伤的影响。雄性 Wistar 大鼠(n=42)分为假手术组、对照组和治疗组,分别注射舒马曲坦(0.1、0.3 和 1mg/kg)、GR-127935(0.01mg/kg)-5-HT1B/1D 受体拮抗剂和舒马曲坦(0.1mg/kg)+GR-127935(0.01mg/kg)。通过顺时针方向旋转右侧睾丸 720 度,使右侧睾丸扭转 1 小时,然后在复位 7 天后进行双侧睾丸切除术。睾丸扭转/复位后,睾丸组织中 TNF-α 水平升高,舒马曲坦注射明显降低了同侧(扭转)和对侧(未扭转)睾丸的 TNF-α 水平(p<0.001)。此外,睾丸扭转/复位后,SOD 活性降低,而舒马曲坦给药显著增加了双侧睾丸的 SOD 活性(p<0.001)。睾丸扭转/复位后,宏观和组织学分析也显示出严重的损伤,舒马曲坦注射改善了这些损伤。有趣的是,舒马曲坦与 GR-127935 联合给药逆转了舒马曲坦对宏观外观、微观形态和生化标志物的有益影响。综上所述,舒马曲坦可能通过刺激 5-HT 受体,减轻缺血再灌注损伤引起的睾丸扭转/复位后炎症、氧化应激和恶化。

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