Testicular ischaemia reperfusion (I/R) injury results with serious dysfunctions in testis. This study aims to explore effects of soluble guanylate cyclase (sGC) stimulator Riociguat on experimental testicular I/R injury in rats. Twenty-one male rats were divided into three groups (Control, IR and IRR). The control group was not exposed to any application. Bilateral testis from IR and IRR animals were rotated 720° in opposite directions for 3 h to induce experimental testicular ischaemia. Animals in IR and IRR groups were subjected to 3 h of reperfusion. Isotonic and Riociguat were administered to the animals 30 min prior reperfusion by oral gavage. At the end of experiment, animals were sacrificed and tissue samples were used for analyses. Riociguat treatment significantly decreased tissue malondialdehyde and Luminol levels compared to the IR group (p < 0.05). The pathological changes, pro-apoptotic proteins (Bax, Caspase 3, and Caspase 9) and apoptotic index in the IR group were down regulated in Riociguat treated animals (p < 0.05). Riociguat treatment was also significantly increased anti-apoptotic Bcl-2 expression, but alleviated tissue injury via modulating pro-inflammatory cytokine IL-1β levels and significantly (p < 0.05) down-regulating NF-κB activity. Moreover, mTOR and ERK phosphorylation increased in IR group (p < 0.05), but Riociguat treatment reduced protein phosphorylation. Our experiment indicated that targeting sGC might support surgical interventions in testicular I/R injury by modulating oxidative stress, inflammation, and apoptotic protein expression levels, but more detailed studies are required to explore the protective activity of Riociguat and underlying mechanisms in testicular I/R injury.

中文翻译：

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Riociguat 靶向可溶性鸟苷酸环化酶可通过调节多种细胞通路减轻睾丸缺血再灌注损伤

睾丸缺血再灌注 (I/R) 损伤导致睾丸严重功能障碍。本研究旨在探讨可溶性鸟苷酸环化酶 (sGC) 刺激剂 Riociguat 对大鼠实验性睾丸 I/R 损伤的影响。将 21 只雄性大鼠分为三组（对照组、IR 组和 IRR 组）。对照组不接触任何应用程序。将 IR 和 IRR 动物的双侧睾丸沿相反方向旋转 720° 3 小时，以诱导实验性睾丸缺血。IR 和 IRR 组的动物接受 3 小时的再灌注。在再灌注前 30 分钟通过口服强饲法对动物施用等渗剂和 Riociguat。在实验结束时，处死动物并将组织样本用于分析。p  < 0.05）。IR 组的病理变化、促凋亡蛋白（Bax、Caspase 3 和 Caspase 9）和凋亡指数在 Riociguat 处理的动物中下调（p  < 0.05）。Riociguat 治疗也显着增加抗凋亡 Bcl-2 表达，但通过调节促炎细胞因子 IL-1β 水平和显着 ( p  < 0.05) 下调 NF-κB 活性减轻组织损伤。此外，IR 组的 mTOR 和 ERK 磷酸化增加（p < 0.05)，但 Riociguat 处理降低了蛋白质磷酸化。我们的实验表明，靶向 sGC 可能通过调节氧化应激、炎症和凋亡蛋白表达水平支持睾丸 I/R 损伤的手术干预，但需要更详细的研究来探索 Riociguat 的保护活性和睾丸 I/R 的潜在机制受伤。