GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats

被引：44
作者：
Hu, Bo [1 ]
Wu, Yuhong [1 ]
Liu, Jie [1 ]
Shen, Xiaohua [1 ]
Tong, Fei [2 ,3 ]
Xu, Guangtao [2 ,3 ]
Shen, Ruilin [1 ]
机构：
[1] Zhejiang Chinese Med Univ, Dept Pathol & Nephrol, Jiaxing Hosp Tradit Chinese Med, Jiaxing, Zhejiang, Peoples R China
[2] Jiaxing Univ, Coll Med, Dept Pathol, Jiaxing, Zhejiang, Peoples R China
[3] Jiaxing Univ, Coll Med, Prov Key Discipline Pharmacol, Jiaxing, Zhejiang, Peoples R China
来源：
KIDNEY & BLOOD PRESSURE RESEARCH | 2016年 / 41卷 / 06期
关键词：
GSK-3beta inhibitor; Renal ischemia/reperfusion injury; Nrf2; TrxR2; Diabetes mellitus; ISCHEMIA-REPERFUSION INJURY; ACUTE KIDNEY INJURY; NF-KAPPA-B; OXIDATIVE STRESS; THIOREDOXIN REDUCTASE; REDOX BALANCE; NECROSIS; KINASE; NRF2; ACTIVATION;
D O I：
10.1159/000452598
中图分类号：
Q4 [生理学];
学科分类号：
071003 ;
摘要：
Background/Aims: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3 beta inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model. Methods: A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2. TrxR2 and caspase-3 expressions in rat kidney tissues were determined. Results: Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats. Conclusion: TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM. (C) 2016 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码：937 / 946
页数：10
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