Targeting HO-1 by Epigallocatechin-3-Gallate Reduces Contrast-Induced Renal Injury via Anti-Oxidative Stress and Anti-Inflammation Pathways.
Targeting HO-1 by Epigallocatechin-3-Gallate Reduces Contrast-Induced Renal Injury via Anti-Oxidative Stress and Anti-Inflammation Pathways.
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表没食子儿茶素-3-没食子酸酯靶向 HO-1 可通过抗氧化应激和抗炎途径减少造影剂引起的肾损伤
DOI：
10.1371/journal.pone.0149032
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zeng C
中科院分区：
文献类型：
--
作者：
Gao Z;Han Y;Hu Y;Wu X;Wang Y;Zhang X;Fu J;Zou X;Zhang J;Chen X;Jose PA;Lu X;Zeng C
氧化应激和炎症共同参与了造影剂肾病的发病过程。表没食子儿茶素没食子酸酯(EGCG)是从绿茶中提纯的儿茶素，具有抗氧化和抗炎作用。然而，EGCG在治疗CIN方面是否有效尚不清楚。我们目前的研究发现，静脉注射EGCG，无论是在CIN建立之前或之后，都具有保护作用，其结果是血清肌酐和血尿素氮水平正常化，肾脏组织病理学评分改善，细胞凋亡减轻，同时氧化应激和炎症反应减少。由于EGCG是抗氧化剂血红素加氧酶-1(HO-1)的有效诱导剂，我们研究了HO-1在CIN中的信号转导。HO-1水平在CIN中升高；EGCG治疗进一步增加HO-1水平，同时伴随着抗氧化蛋白调节因子Nrf2的增加。有趣的是，用原卟啉IX锌(II)阻断HO-1可阻断EGCG对CIN的保护作用。锌PP还阻断了EGCG增加抗氧化剂(超氧化物歧化酶)活性的能力，降低了氧化应激(髓过氧化物酶和丙二醛)和炎症(髓过氧化物酶和IL-1β)的标记物，表明HO-1是调节EGCG介导的保护的上游分子。为了进一步确定HO-1在EGCG介导的炎症抑制中的作用，我们研究了EGCG对IL-1β上游信号NLRP3炎症小体的影响。EGCG下调NLRP3的表达，其表达被ZnPP阻断，表明HO-1将EGCG与NLRP3联系在一起。因此，EGCG通过上调HO-1，通过改善氧化应激和炎症来保护CIN。
Both oxidative stress and inflammation are involved in the pathogenesis of contrast-induced nephropathy (CIN). Epigallocatechin-3-gallate (EGCG), a purified catechin from green tea, has antioxidant and anti-inflammatory effects. However, it is unknown whether or not EGCG is effective in treating CIN. Our present study found that intravenous administration of EGCG, either before or just after the establishment of CIN, had a protective effect, determined by normalization of serum creatinine and blood urea nitrogen levels, improvement in renal histopathological scoring and alleviation of apoptosis, accompanied by decreased oxidative stress and inflammation. Because EGCG is a potent inducer of the antioxidant heme oxygenase-1 (HO-1), we studied HO-1 signaling in CIN. HO-1 levels were increased in CIN; treatment with EGCG further increased HO-1 levels, accompanied by an increase in Nrf2, a regulator of antioxidant proteins. Interestingly, blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) prevented the protective effect of EGCG on CIN. ZnPP also blocked the ability of EGCG to increase the activity of an antioxidant (superoxide dismutase), and decrease markers of oxidative stress (myeloperoxidase and malondialdehyde) and inflammation (myeloperoxidase and IL-1β), indicating that HO-1 is the upstream molecule that regulates the EGCG-mediated protection. To determine further the role of HO-1 on the EGCG-mediated inhibition of inflammation, we studied the effect of EGCG on the NLRP3 inflammasome, an upstream signaling of IL-1β. EGCG down-regulated NLRP3 expression, which was blocked by ZnPP, indicating that HO-1 links EGCG with NLRP3. Therefore, EGCG, via up-regulation of HO-1, protects against CIN by amelioration of oxidative stress and inflammation.