The green tea polyphenol (-)-epigallocatechin-3-gallate ameliorates experimental immune-mediated glomerulonephritis
The green tea polyphenol (-)-epigallocatechin-3-gallate ameliorates experimental immune-mediated glomerulonephritis
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DOI：
10.1038/ki.2011.121
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发表时间：
2011-09-01
影响因子：
19.6
通讯作者：
Zhou, Xin J.
中科院分区：
文献类型：
--
作者：
Peng, Ai;Ye, Ting;Zhou, Xin J.
炎症细胞过度产生活性氧和活性氮可导致组织损伤，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，我们测试了绿色茶多酚（-）-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的发展有有利的影响。从诱导GN前2天至诱导GN后2周，用EGCG预处理129/svJ小鼠，导致蛋白尿和血清肌酐减少，与溶剂预处理的患病小鼠相比，肾组织学显著改善。这种预处理降低了氧化应激，并使骨桥蛋白、p65/核因子-jB、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、p47 phox和髓过氧化物酶正常化，所有这些在溶媒预处理的患病小鼠中均升高。谷胱甘肽过氧化物酶和过氧化物酶体增殖物激活受体-c（PPARc）的水平，两者都降低了车辆预处理的患病小鼠，正常化。在整个EGCG预处理期间，通过伴随施用PPARc拮抗剂GW 9662逆转这种肾保护作用。重要的是，即使在GN发作后1周开始多酚治疗，死亡率和肾功能障碍也显着减弱。因此，EGCG通过靶向氧化还原和炎症途径逆转了小鼠免疫介导的GN的进展。Kidney International（2011）80，601-611; doi：10.1038/ki.2011.121; 2011年5月4日在线发表
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-jB, 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-c (PPARc), both reduced in the vehicle-pretreated diseased mice, were normalized. This renoprotective effect was reversed by concomitant administration of the PPARc 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. Kidney International (2011) 80, 601-611; doi: 10.1038/ki.2011.121;published online 4 May 2011