Xie D-Q, Sun G-Y, Zhang X-G, Gan H
Division of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Division of Nephrology, Yibin Second People's Hospital, Yibin, China.
Division of Nephrology, Yibin Second People's Hospital, Yibin, China.
Transplant Proc. 2015 Jul-Aug;47(6):1620-6. doi: 10.1016/j.transproceed.2015.06.011.
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms of renal I/R injury involve inflammation, oxidative stress, and apoptosis. Osthole, a natural coumarin derivative, has potential anti-inflammatory effects. This study investigated the effect of osthole on renal I/R injury and its potential mechanism.
We induced renal I/R injury by clamping the left renal artery for 45 min followed by reperfusion, along with a contralateral nephrectomy. We randomly assigned 30 rats to 3 groups (n = 10): sham-operated, vehicle-treated I/R, and osthole-treated I/R. We treated rats intra-peritoneally with osthole (40 mg/kg) or vehicle (40 mg/kg) 45 min before renal ischemia. We harvested serum and kidneys at 24 h after reperfusion. Renal function and histological changes were assessed. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in renal tissue and serum were examined by means of RT-PCR and ELISA, respectively. The expression of p-p85, p85, p-Akt, Akt, p-p65, and p65 were measured by means of Western blotting.
Osthole pre-treatment significantly attenuated renal dysfunction, renal histological changes, NF-κB activation, and the expression of TNF-α, IL-8, and IL-6 induced by I/R injury, but the activation of PI3K/Akt signaling was further increased.
Osthole pre-treatment protects rats against renal I/R injury by suppressing NF-κB activation, which is involved in PI3K/Akt signaling activation. Thus, osthole may be a novel practical strategy to prevent renal I/R injury.
肾缺血再灌注(I/R)损伤是急性肾损伤的主要原因。肾I/R损伤的发病机制涉及炎症、氧化应激和细胞凋亡。蛇床子素是一种天然香豆素衍生物,具有潜在的抗炎作用。本研究探讨了蛇床子素对肾I/R损伤的影响及其潜在机制。
通过夹闭左肾动脉45分钟后再灌注并进行对侧肾切除术诱导肾I/R损伤。将30只大鼠随机分为3组(每组n = 10):假手术组、溶剂处理的I/R组和蛇床子素处理的I/R组。在肾缺血前45分钟,给大鼠腹腔注射蛇床子素(40 mg/kg)或溶剂(40 mg/kg)。再灌注24小时后收集血清和肾脏。评估肾功能和组织学变化。分别通过RT-PCR和ELISA检测肾组织和血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)和白细胞介素-6(IL-6)的表达。通过蛋白质印迹法检测p-p85、p85、p-Akt、Akt、p-p65和p65的表达。
蛇床子素预处理显著减轻了I/R损伤诱导的肾功能障碍、肾组织学变化、NF-κB激活以及TNF-α、IL-8和IL-6的表达,但PI3K/Akt信号通路的激活进一步增加。
蛇床子素预处理通过抑制参与PI3K/Akt信号通路激活的NF-κB激活来保护大鼠免受肾I/R损伤。因此,蛇床子素可能是预防肾I/R损伤的一种新的实用策略。