Wang Yanqiu, Wang Bowen, Du Feng, Su Xuesong, Sun Guangping, Zhou Guangyu, Bian Xiaohui, Liu Na
Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
Basic Clin Pharmacol Toxicol. 2015 Sep;117(3):164-72. doi: 10.1111/bcpt.12383. Epub 2015 Feb 19.
Oxidative stress and inflammation contribute importantly to the pathogenesis of chronic kidney disease (CKD). Epigallocatechin-3-gallate (EGCG), which is the most abundant and most active catechin polyphenol extracted from green tea, has been proved to have many bioactivities. In this study, the renoprotective effect of EGCG was evaluated in a widely used kidney disease model, the unilateral ureteral obstruction (UUO) mice model. After 14 days of EGCG administration, mean arterial blood pressure, body-weight and obstructed kidney weight were measured. Levels of blood urea nitrogen (BUN) and creatinine (CR) and activities of glutamic-pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) in serum were estimated as indicators of renal function. Periodic acid-Schiff (PAS) staining was performed to observe the pathological changes of the obstructed kidney. Antioxidant enzymes and pro-inflammatory cytokine production were estimated to reflect the oxidative stress and inflammatory state in the obstructed kidney. Finally, the main proteins in the NF-κB and Nrf2 signalling pathway and DNA binding activity of NF-κB and Nrf2 were measured to investigate the effect of EGCG on these two pathways. The results demonstrated that EGCG could restore UUO-induced kidney weight loss and renal dysfunction. In addition, UUO-induced oxidative stress and inflammatory responses in the obstructed kidney were also prevented by EGCG. Furthermore, EGCG could induce both NF-κB and Nrf2 nuclear translocation in the UUO kidney and promote heme oxygenase-1 (HO-1) production. These results indicated that the renoprotective effect of EGCG might be through its NF-κB and Nrf2 signalling pathway regulations.
氧化应激和炎症在慢性肾脏病(CKD)的发病机制中起重要作用。表没食子儿茶素-3-没食子酸酯(EGCG)是从绿茶中提取的含量最丰富、活性最强的儿茶素多酚,已被证明具有多种生物活性。在本研究中,在一种广泛应用的肾脏疾病模型——单侧输尿管梗阻(UUO)小鼠模型中评估了EGCG的肾脏保护作用。给予EGCG 14天后,测量平均动脉血压、体重和梗阻侧肾脏重量。测定血清中尿素氮(BUN)和肌酐(CR)水平以及谷丙转氨酶(GPT)和乳酸脱氢酶(LDH)活性作为肾功能指标。进行过碘酸希夫(PAS)染色以观察梗阻侧肾脏的病理变化。评估抗氧化酶和促炎细胞因子的产生以反映梗阻侧肾脏的氧化应激和炎症状态。最后,检测NF-κB和Nrf2信号通路中的主要蛋白以及NF-κB和Nrf2的DNA结合活性,以研究EGCG对这两条通路的影响。结果表明,EGCG可恢复UUO诱导的肾脏重量减轻和肾功能障碍。此外,EGCG还可预防UUO诱导的梗阻侧肾脏氧化应激和炎症反应。此外,EGCG可诱导UUO肾脏中NF-κB和Nrf2核转位,并促进血红素加氧酶-1(HO-1)的产生。这些结果表明,EGCG的肾脏保护作用可能是通过其对NF-κB和Nrf2信号通路的调节实现的。