Abstract
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.
Highlights
Sepsis, an infection induced systemic inflammatory response syndrome (SIRS), has become the leading cause of mortality in the intensive care unit (ICU) worldwide [1, 2]
The results demonstrated that resveratrol significantly improved the renal function and tubular epithelial cell injury and enhanced the survival rate of cecal ligation and puncture (CLP)-induced rat model of sepsis, which was accompanied by a substantial decrease of the serum content and renal mRNA expressions of tumor necrosis factor-α (TNF-α), IL-1β and IL-6
To determine the effect of resveratrol on sepsis-induced acute kidney injury (AKI), a rat model of polymicrobial sepsis was established by CLP operation
Summary
An infection induced systemic inflammatory response syndrome (SIRS), has become the leading cause of mortality in the intensive care unit (ICU) worldwide [1, 2]. It is caused by various etiological factors and can result in multiple organ dysfunctions (MODS) because of lasting and uncontrolled inflammatory response. Targeted therapies on some specific inflammatory factors show little improvement on the prognosis of sepsis, the mortality still remains unacceptably high. Once the patients suffer from severe sepsis complicated with AKI, the mortality can rise up to 70% [3]. Exploring novel targets and strategies that can ameliorate septic AKI is still of great importance
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