Epigallocatechin-3-gallate protects kidneys from ischemia reperfusion injury by HO-1 upregulation and inhibition of macrophage infiltration
Epigallocatechin-3-gallate protects kidneys from ischemia reperfusion injury by HO-1 upregulation and inhibition of macrophage infiltration
复制标题
DOI：
10.1111/j.1432-2277.2011.01224.x
复制
发表时间：
2011-05-01
影响因子：
3.1
通讯作者：
Nonomura, Norio
中科院分区：
文献类型：
--
作者：
Kakuta, Yoichi;Okumi, Masayoshi;Nonomura, Norio
P>表没食子儿茶素-3-没食子酸酯 (EGCG) 显示出多种化学和生物活性。我们研究了 EGCG 在大鼠肾缺血再灌注 (I/R) 损伤模型中的作用。 Sprague-Dawley 大鼠在 I/R 损伤前 48 小时、24 小时和 30 分钟腹腔注射 50 mg/kg EGCG。对动物进行左肾闭塞45分钟。 EGCG 治疗抑制了血清肌酐的峰值。经 EGCG 处理的肾脏显示肾小管损伤明显减少，凋亡细胞数量减少。 EGCG 组中 I/R 引起的肾脏 MDA 水平升高显着降低。逆转录酶聚合酶链反应显示，EGCG 显着降低 MHC II 类、TLR2、TLR4、MCP-1、IL-18、TGF-β 1、前胶原 Ia1、TIMP-1 和 Kim-1 的表达。 ED-1 染色显示巨噬细胞浸润减少，α-SMA 染色显示间质表达减少。根据 RT-PCR 和蛋白质印迹分析的结果，EGCG 组 I/R 肾脏中的血红素加氧酶-1 (HO-1) 表达上调。 SnPP 阻断 HO-1 基因诱导会增加肾小管损伤和巨噬细胞浸润。这些发现表明，EGCG 通过减少巨噬细胞浸润和减少肾纤维化来保护肾脏免受 I/R 损伤。这些有益作用可能部分是通过 HO-1 基因的增强来介导的。
P>Epigallocatechin-3-gallate (EGCG) shows diverse chemical and biological activities. We investigated the effects of EGCG in a rat renal ischemia reperfusion (I/R) injury model. Sprague-Dawley rats received intraperitoneal injection of 50 mg/kg EGCG 48 h, 24 h, and 30 min prior to I/R injury. The animals were subjected to left renal occlusion for 45 min. EGCG treatment suppressed the peak in serum creatinine. EGCG-treated kidneys showed significantly less tubular damage and a decreased number of apoptotic cells. The I/R-induced elevation in the renal MDA level was significantly decreased in the EGCG group. Reverse-transcriptase polymerase chain reaction showed that EGCG significantly decreased the expression of MHC class II, TLR2, TLR4, MCP-1, IL-18, TGF-beta 1, procollagen Ia1, TIMP-1, and Kim-1. ED-1 staining showed reduced macrophage infiltration and alpha-SMA staining revealed less interstitial expression. Heme oxygenase-1 (HO-1) expression in I/R kidneys was upregulated in the EGCG group based on the results of both RT-PCR and Western blotting analysis. Blockade of HO-1 gene induction by SnPP increased renal tubular damage and macrophage infiltration. These findings suggest that EGCG protects the kidneys against I/R injury by reducing macrophage infiltration and decreasing renal fibrosis. These beneficial effects may be mediated, in part, by augmentation of the HO-1 gene.