Department of Nephrology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
Kidney Int. 2011 Sep;80(6):601-11. doi: 10.1038/ki.2011.121. Epub 2011 May 4.
The unchecked overproduction of reactive oxygen and nitrogen species by inflammatory cells can cause tissue damage, intensify inflammation, promote apoptosis, and accelerate the progression of immune-mediated glomerulonephritis (GN). Here we tested whether the anti-inflammatory and antioxidant properties of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) favorably affect the development of immune-mediated GN. Pretreatment of 129/svJ mice with EGCG from 2 days before to 2 weeks after the induction of GN led to reduced proteinuria and serum creatinine, and marked improvement in renal histology when compared with vehicle-pretreated diseased mice. This pretreatment reduced oxidative stress, and normalized osteopontin, p65/nuclear factor-κB, inducible nitric oxide synthase, nitric oxide metabolites, p-Akt, phosphorylated extracellular signal-regulated kinases 1 and 2, p47phox, and myeloperoxidase, all of which were elevated in vehicle-pretreated diseased mice. Levels of glutathione peroxidase and peroxisome proliferator-activated receptor-γ (PPARγ), both reduced in the vehicle-pretreated diseased mice, were normalized. This renoprotective effect was reversed by concomitant administration of the PPARγ antagonist GW9662 throughout the EGCG pretreatment period. Importantly, mortality and renal dysfunction were significantly attenuated even when the polyphenol treatment was initiated 1 week after the onset of GN. Thus, EGCG reversed the progression of immune-mediated GN in mice by targeting redox and inflammatory pathways.
炎症细胞中活性氧和活性氮物种的不受控制的过度产生会导致组织损伤、加剧炎症、促进细胞凋亡，并加速免疫介导的肾小球肾炎（GN）的进展。在这里，我们测试了绿茶多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）的抗炎和抗氧化特性是否对免疫介导的 GN 的发展产生有利影响。与用载体预处理的患病小鼠相比，在 GN 诱导前 2 天至诱导后 2 周用 EGCG 预处理 129/svJ 小鼠可减少蛋白尿和血清肌酐，并显著改善肾脏组织学。这种预处理减少了氧化应激，并使骨桥蛋白、p65/核因子-κB、诱导型一氧化氮合酶、一氧化氮代谢物、p-Akt、磷酸化细胞外信号调节激酶 1 和 2、p47phox 和髓过氧化物酶正常化，所有这些在载体预处理的患病小鼠中均升高。在载体预处理的患病小鼠中降低的谷胱甘肽过氧化物酶和过氧化物酶体增殖物激活受体-γ（PPARγ）水平均恢复正常。在 EGCG 预处理期间同时给予 PPARγ 拮抗剂 GW9662 可逆转这种肾保护作用。重要的是，即使在 GN 发病后 1 周开始多酚治疗，也显著减轻了死亡率和肾功能障碍。因此，EGCG 通过靶向氧化还原和炎症途径逆转了小鼠的免疫介导的 GN 进展。
