Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
PLoS One. 2023 Oct 26;18(10):e0287987. doi: 10.1371/journal.pone.0287987. eCollection 2023.
Testicular torsion is a urological emergency. However, surgical detorsion of the torsed spermatic cord can cause testicular reperfusion injury. Although remote ischemic preconditioning (RIPC) has been convincingly shown to protect organs against ischemia/reperfusion (I/R) injury, little is known regarding the effect of RIPC on testicular torsion/detorsion-induced reperfusion injury. Therefore, we aimed to evaluate the effect of RIPC on testes after testicular I/R injury in a rat model in vivo. Male Sprague-Dawley rats were randomly classified into 4 groups: sham-operated (sham), testicular I/R (TI/R), or remote liver (RIPC liver) and limb (RIPC limb) ischemic preconditioning groups. Testis I/R was induced by 3 h of right spermatic cord torsion (720° clockwise), and reperfusion was allowed for 3 hours. In the RIPC group, four cycles of 5 min of ischemia and 5 min of reperfusion were completed 30 min prior to testicular torsion. The ERK1/2 inhibitor U0126 was administered intravenously at the beginning of reperfusion (1 mg/kg). The testes were taken for the oxidative stress evaluations, histology, apoptosis, immunohistochemical and western blotting analysis. Remote liver and limb ischemic preconditioning attenuated ipsilateral and contralateral testicular damage after testicular I/R injury. For example. RIPC reduced testicular swelling and oxidative stress, lessened structural damage, and inhibited the testicular inflammatory response and apoptosis. Furthermore, RIPC treatment enhanced testicular ERK1/2 phosphorylation postI/R. Inhibition of ERK1/2 activity using U0126 eliminated the protection offered by RIPC. Our data demonstrate for the first time that RIPC protects testes against testicular I/R injury via activation of the ERK1/2 signaling pathway.
睾丸扭转是一种泌尿外科急症。然而,精索扭转的手术复位可能会导致睾丸再灌注损伤。虽然远隔缺血预处理(RIPC)已被证实可保护器官免受缺血/再灌注(I/R)损伤,但关于 RIPC 对睾丸扭转/复位引起的再灌注损伤的影响知之甚少。因此,我们旨在体内大鼠模型中评估 RIPC 对睾丸 I/R 损伤后的影响。雄性 Sprague-Dawley 大鼠随机分为 4 组:假手术(sham)、睾丸 I/R(TI/R)、远隔肝脏(RIPC liver)和肢体(RIPC limb)缺血预处理组。通过 3 小时的右侧精索扭转(顺时针 720°)诱导睾丸 I/R,允许再灌注 3 小时。在 RIPC 组中,在睾丸扭转前 30 分钟完成 4 个周期的 5 分钟缺血和 5 分钟再灌注。在再灌注开始时静脉注射 ERK1/2 抑制剂 U0126(1 mg/kg)。取睾丸进行氧化应激评估、组织学、细胞凋亡、免疫组化和 Western blot 分析。远隔肝脏和肢体缺血预处理可减轻睾丸 I/R 损伤后的同侧和对侧睾丸损伤。例如,RIPC 减少了睾丸肿胀和氧化应激,减轻了结构损伤,抑制了睾丸炎症反应和细胞凋亡。此外,RIPC 处理增强了再灌注后睾丸 ERK1/2 的磷酸化。使用 U0126 抑制 ERK1/2 活性消除了 RIPC 提供的保护。我们的数据首次表明,RIPC 通过激活 ERK1/2 信号通路来保护睾丸免受睾丸 I/R 损伤。