Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510660, China.
Department of Nephrology, Pinghu Hospital, Health Science Center, South China Hospital of Shenzhen University, Shenzhen 518116, China.
Biomed Res Int. 2022 Mar 28;2022:7140961. doi: 10.1155/2022/7140961. eCollection 2022.
The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model.
A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed.
RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF-, CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF-Bp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-Bp65.
SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF-B signaling pathway.
提高接受肾移植患者的长期存活率仍然具有挑战性。缺血再灌注损伤（IRI）会降低移植后早期的长期肾移植物存活率。然而，很少有研究调查 IRI 对慢性肾移植物衰竭发病机制的影响。沉默信息调节因子 1（SIRT1）调节抗氧化应激和炎症反应，并可预防 IRI。本研究旨在研究 SIRT1 激活剂白藜芦醇（RSV）在预防大鼠肾移植模型肾损伤中的作用。
建立经典的 F334 至 LEW 原位肾移植大鼠模型。实验组从肾移植前三天开始接受 RSV 治疗，治疗持续到收获日。进行单侧肾切除术的 F344 和 Lewis 大鼠被用作对照。12 周后，根据肾功能、组织病理学、免疫组织化学和 Western blot 评估 RSV 的作用。还评估了氧化应激相关标志物和促炎细胞因子的活性。
RSV 治疗可显著改善肾移植大鼠的肾功能和组织病理学损伤，增加 GSH、SOD 和 CAT 的水平，降低 MDA 和 iNOS 的水平。此外，RSV 还抑制了肾移植大鼠中促炎细胞因子/趋化因子（如 TNF-α、CD68 和 IL-6）的表达。此外，移植组的 SIRT1 水平明显较低，Ac-NF-Bp65 水平较高。RSV 增加了 SIRT1 的表达，降低了 Ac-NF-Bp65 的表达。
SIRT1 在慢性肾移植功能障碍的发病机制中起重要作用。通过激活 SIRT1/NF-B 信号通路，它是一种改善肾移植后炎症和氧化应激诱导的肾损伤的潜在治疗剂。
