Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway.
Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway.
复制标题
白藜芦醇通过抑制内质网应激激活的 NF-κ B 通路，预防早期多种微生物脓毒症引起的急性肾损伤
DOI：
10.18632/oncotarget.16860
复制
发表时间：
2017-05-30
期刊：
影响因子：
--
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Wang N;Mao L;Yang L;Zou J;Liu K;Liu M;Zhang H;Xiao X;Wang K
白藜芦醇是一种来源于各种可食用植物的多酚化合物，通过其抗炎活性防止脓毒症诱导的急性肾损伤（阿基），但其潜在机制仍不清楚。本研究采用盲肠结扎穿孔（CLP）法建立大鼠脓毒症模型，CLP术后立即腹腔注射白藜芦醇30 mg/kg。用1 μg/ml脂多糖、0.2 μM衣霉素、2.5mM伊司他丁9389和20 μM白藜芦醇处理HK-2细胞用于体外研究。结果表明，白藜芦醇能显著改善CLP诱导的脓毒症大鼠肾功能和肾小管上皮细胞损伤，提高存活率，并能显著降低血清TNF-α、IL-1β和IL-6的含量及肾组织TNF-α、IL-1β和IL-6的mRNA表达。此外，白藜芦醇还能明显减轻内质网应激，抑制肾脏肌醇需要酶1（IRE 1）和核因子-κB（NF-κB）的磷酸化。体外研究表明，白藜芦醇可通过抑制IRE 1的活化，提高HK-2细胞的存活率，减少NF-κB的磷酸化和炎症因子的产生。综上所述，脓毒症发作后尽快给予白藜芦醇可主要通过抑制肾脏中IRE 1-NF-κB通路触发的炎症反应来预防脓毒症阿基。白藜芦醇可能是一个容易翻译的选择，以改善脓毒症的预后。
Resveratrol, a polyphenol compound derived from various edible plants, protects against sepsis-induced acute kidney injury (AKI) via its anti-inflammatory activity, but the underlying mechanisms remain largely unknown. In this study, a rat model of sepsis was established by cecal ligation and puncture (CLP), 30 mg/kg resveratrol was intraperitoneally administrated immediately after the CLP operation. HK-2 cells treated by 1 μg/ml lipopolysaccharide, 0.2 μM tunicamycin, 2.5 mM irestatin 9389 and 20 μM resveratrol were used for in vitro study. The results demonstrated that resveratrol significantly improved the renal function and tubular epithelial cell injury and enhanced the survival rate of CLP-induced rat model of sepsis, which was accompanied by a substantial decrease of the serum content and renal mRNA expressions of TNF-α, IL-1β and IL-6. In addition, resveratrol obviously relieved the endoplasmic reticulum stress, inhibited the phosphorylation of inositol-requiring enzyme 1(IRE1) and nuclear factor-κB (NF-κB) in the kidney. In vitro studies showed that resveratrol enhanced the cell viability, reduced the phosphorylation of NF-κB and production of inflammatory factors in lipopolysaccharide and tunicamycin-induced HK-2 cells through inhibiting IRE1 activation. Taken together, administration of resveratrol as soon as possible after the onset of sepsis could protect against septic AKI mainly through inhibiting IRE1-NF-κB pathway-triggered inflammatory response in the kidney. Resveratrol might be a readily translatable option to improve the prognosis of sepsis.