促红细胞生成素通过靶向 AMPK/Nox4/ROS 通路抑制肾缺血再灌注损伤中的氧化应激。
Suppressive effect erythropoietin on oxidative stress by targeting AMPK/Nox4/ROS pathway in renal ischemia reperfusion injury.
机构信息
Queen Mary School, Nanchang University, Nanchang 330031, China.
Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences & Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Disease, Chengdu 610072, China.
出版信息
Transpl Immunol. 2022 Jun;72:101537. doi: 10.1016/j.trim.2022.101537. Epub 2022 Jan 11.
OBJECTIVE
To explore the effect of erythropoietin (EPO) on the AMP-activated protein kinase (AMPK)/nicotinamide adenine dinucleotide phosphatase oxidase 4 (NOX4) signaling pathway during renal ischemia reperfusion injury (RIRI) in rats.
METHODS
A rat model of RIRI was established by clamping the left renal pedicle and removing the right kidney. The rats in the sham group did not have their left renal pedicle clamped. Rats with a model of RIRI were randomly divided into RIRI alone (control), erythropoietin treatment (EPO/RIRI), and Compound C treatment (CPC/RIRI) groups. Hematoxylin-eosin (H&E) staining was used to examine pathological kidney damage. Serum creatinine and urea nitrogen levels were measured to evaluate renal function. Western blotting was performed to detect the expression levels of phosphorylated p-AMPK and total AMPK protein in the kidneys. RT-PCR was used to evaluate the mRNA levels of Nox4 and p22 in the kidneys. Oxidative stress-related indices (ROS, CAT, GSH, SOD, and MDA) were also measured.
RESULTS
EPO treatment improved kidney function by preventing kidney damage induced by the RIRI model. Preventing ischemia/reperfusion injury in the RIRI model was correlated with an increased p-AMPK/AMPK ratio and elevated activity of CAT, GSH, and SOD, which ameliorated the expression of NOX4, p22, ROS, and MDA. Moreover, treatment with CPC (an AMPK inhibitor) reduced the effects of EPO in the RIRI model.
CONCLUSION
EPO treatment protected rats against RIRI in the RIRI model by alleviating oxidative stress by triggering the AMPK/NOX4/ROS pathway.
目的
探讨促红细胞生成素（EPO）对大鼠肾缺血再灌注损伤（RIRI）中 AMP 激活的蛋白激酶（AMPK）/烟酰胺腺嘌呤二核苷酸磷酸酶氧化酶 4（NOX4）信号通路的影响。
方法
通过夹闭左肾蒂和切除右肾建立大鼠 RIRI 模型。假手术组大鼠不夹闭左肾蒂。RIRI 模型大鼠随机分为 RIRI 组（对照）、EPO 治疗组（EPO/RIRI）和化合物 C 治疗组（CPC/RIRI）。苏木精-伊红（H&E）染色观察肾脏病理损伤。检测血清肌酐和尿素氮水平评估肾功能。Western blot 检测肾脏磷酸化 p-AMPK 和总 AMPK 蛋白表达水平。RT-PCR 检测肾脏 Nox4 和 p22mRNA 表达水平。还测量了氧化应激相关指标（ROS、CAT、GSH、SOD 和 MDA）。
结果
EPO 治疗通过防止 RIRI 模型引起的肾损伤改善了肾功能。在 RIRI 模型中，预防缺血/再灌注损伤与 p-AMPK/AMPK 比值增加和 CAT、GSH 和 SOD 活性升高相关，从而改善了 NOX4、p22、ROS 和 MDA 的表达。此外，用 CPC（一种 AMPK 抑制剂）处理降低了 EPO 在 RIRI 模型中的作用。
结论
EPO 通过触发 AMPK/NOX4/ROS 通路减轻氧化应激，从而保护大鼠免受 RIRI 模型中的 RIRI。
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