Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4547-4553. doi: 10.3892/mmr.2018.8450. Epub 2018 Jan 17.
Remote ischemic preconditioning (RIPC) is a minimally invasive method that provides protection by reducing injury to the heart, kidneys, brain and other tissues or organs. RIPC may improve the outcome in patients undergoing surgery. Although the role of RIPC has been studied, the results remain controversial. It is difficult to confirm whether RIPC has a kidney protective effect and the understanding of the preconditioning signal pathway involved remains unclear. In the present study, the effect of RIPC in urology was evaluated. The protection against renal damage was assessed by investigating the potential mediator, hypoxia‑inducible factor‑1α (HIF‑1α), and the functional adrenomedullin (ADM) pathway. Male Sprague‑Dawley (SD) rats were used in the present study. The animal model of kidney damage induced by ischemia reperfusion (IR) was used to investigate the protective effect of the acute and delayed phase RIPC. Furthermore, the protective effects of RIPC mediated by a HIF‑1α‑ADM pathway were assessed. The indexes of renal function and oxidative damage indicators were measured by Cr, BUN, mALB, β2‑MG, MPO, MDA and SOD assays, and the expression of HIF‑1α and ADM were detected by western blot analysis, immunohistochemistry and ELISA assays. Tubular score, determined using hematoxylin and eosin staining, was used to evaluate renal tissue damage. Applying RIPC prevented IR‑induced renal dysfunction and oxidative damage by decreasing Cr, BUN, mALB, β2‑MG, MPO, MDA levels and increasing SOD activity. Findings showed that delayed RIPC had an improved effect compared with acute treatment. Delayed RIPC also upregulated the expression of HIF‑1α and ADM, indicating that the protective effect of the delayed RIPC may be associated with a HIF‑1α‑ADM‑mediated mechanism. The effect of the delayed RIPC to reduce IR‑induced renal damage and increase ADM expression was enhanced by HIF‑1α agonists DMOG and BAY 85‑3934, whereas the effect was whittled by HIF‑1α antagonists YC‑1 and 2‑MeOE2. Furthermore, receiving ADM also offered protection to the kidney in comparison with the IR+Vehicle group. These findings suggest that RIPC prevents IR‑mediated renal damage by HIF‑1α via an ADM humoral pathway. In the present study, RIPC provided an effective renal protection. ADM could also offer protection regulated by HIF‑1α in renal tissue. However, the mechanism of ADM as a protective factor in RIPC requires further research.
远程缺血预处理（RIPC）是一种微创方法，通过减少心脏、肾脏、大脑和其他组织或器官的损伤来提供保护。RIPC 可能改善接受手术的患者的预后。尽管已经研究了 RIPC 的作用，但结果仍存在争议。难以确定 RIPC 是否具有肾脏保护作用，并且对涉及的预处理信号通路的理解仍不清楚。在本研究中，评估了 RIPC 在泌尿科中的作用。通过研究潜在的介质缺氧诱导因子-1α（HIF-1α）和功能性肾上腺髓质素（ADM）途径来评估对肾脏损伤的保护作用。雄性 Sprague-Dawley（SD）大鼠用于本研究。使用缺血再灌注（IR）诱导的肾脏损伤动物模型来研究急性和延迟相 RIPC 的保护作用。此外，评估了由 HIF-1α-ADM 途径介导的 RIPC 的保护作用。通过 Cr、BUN、mALB、β2-MG、MPO、MDA 和 SOD 测定来测量肾功能和氧化损伤指标，并通过 Western blot 分析、免疫组织化学和 ELISA 测定来检测 HIF-1α和 ADM 的表达。使用苏木精和伊红染色评估肾小管评分，以评估肾脏组织损伤。应用 RIPC 通过降低 Cr、BUN、mALB、β2-MG、MPO、MDA 水平和增加 SOD 活性来预防 IR 诱导的肾功能障碍和氧化损伤。结果表明，与急性治疗相比，延迟 RIPC 具有更好的效果。延迟 RIPC 还上调了 HIF-1α和 ADM 的表达，表明延迟 RIPC 的保护作用可能与 HIF-1α-ADM 介导的机制有关。HIF-1α 激动剂 DMOG 和 BAY 85-3934 增强了延迟 RIPC 降低 IR 诱导的肾脏损伤和增加 ADM 表达的作用，而 HIF-1α 拮抗剂 YC-1 和 2-MeOE2 削弱了这种作用。此外，与 IR+Vehicle 组相比，接受 ADM 也可以对肾脏提供保护。这些发现表明，RIPC 通过 ADM 体液途径通过 HIF-1α 防止 IR 介导的肾脏损伤。在本研究中，RIPC 提供了有效的肾脏保护。ADM 也可以通过 HIF-1α 调节肾脏组织中的保护作用。然而，ADM 作为 RIPC 中保护因子的机制需要进一步研究。
