GSPE Inhibits HMGB1 Release, Attenuating Renal IR-Induced Acute Renal Injury and Chronic Renal Fibrosis.
GSPE Inhibits HMGB1 Release, Attenuating Renal IR-Induced Acute Renal Injury and Chronic Renal Fibrosis.
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GSPE 抑制 HMGB1 释放，减轻肾 IR 引起的急性肾损伤和慢性肾纤维化。
DOI：
10.3390/ijms17101647
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发表时间：
2016-09-29
影响因子：
5.6
通讯作者：
Xu G
中科院分区：
文献类型：
--
作者：
Zhan J;Wang K;Zhang C;Zhang C;Li Y;Zhang Y;Chang X;Zhou Q;Yao Y;Liu Y;Xu G
葡萄籽原花青素提取物（GSPE）是一种从葡萄籽中提取的多酚类化合物，具有抗氧化、抗炎和抗肿瘤等活性。HMGB 1是一种新发现的炎症相关分子模式（DAMP），一旦被坏死细胞释放，具有强效的促炎作用。然而，GSPE对HMGB 1的影响，以及两者与急性肾损伤和慢性肾纤维化的关系尚不清楚。本研究旨在研究GSPE对急性肾损伤和慢性纤维化的影响。对C57 bl/6小鼠进行双侧缺血/再灌注（I/R）和单侧I/R，给予或不给予GSPE。在双侧I/R后，给予GSPE的小鼠在肾功能（BUN和Cr）方面具有显著改善，减少病理损伤并减轻炎症。在单侧I/R中，GSPE处理的小鼠表现出肾小管间质纤维化减少和炎症反应降低。GSPE对两种模型的肾脏保护作用均与抑制HMGB 1核质穿梭和释放有关，HMGB 1核质穿梭和释放可通过与其下游受体TLR 4结合而放大炎症反应，并促进P65转录。因此，我们有理由相信GSPE在临床实践中可能是预防和治疗IR诱导的肾损伤和纤维化的良好替代疗法。
Grape seed proanthocyanindin extract (GSPE) is a polyphenolic bioflavonoid derived from grape seeds and has been widely studied for its potent antioxidant, anti-inflammatory and antitumor activities. HMGB1 is a newly discovered danger-associated molecular pattern (DAMP) that has potent proinflammatory effects once released by necrotic cells. However, the effect of GSPE on the HMGB1, and the relationship of those two with acute kidney injury and chronic kidney fibrosis are unknown. This study aimed to investigate the impact of GSPE on acute kidney injury and chronic fibrosis. C57bl/6 mice were subjected to bilateral ischemia/reperfusion (I/R) and unilateral I/R with or without GSPE administration. After bilateral I/R, mice administered GSPE had a marked improvement in renal function (BUN and Cr), decreased pathological damage and reduced inflammation. In unilateral I/R, mice subjected GSPE showed reduced tubulointerstitial fibrosis and decreased inflammatory reaction. The renoprotection of GSPE on both models was associated with the inhibition of HMGB1 nucleocytoplasmic shuttling and release, which can amplify the inflammation through binding to its downstream receptor TLR4 and facilitated P65 transcription. Thus, we have reason to believe that GSPE could be a good alternative therapy for the prevention and treatment of IR-induced renal injury and fibrosis in clinical practice.
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