Abstract

To evaluate the protective effects of resveratrol on acute kidney injury (AKI) in septic rats. A septic rat model was established by cecal ligation and puncture (CLP). A total of 108 male Sprague Dawley rats were randomly divided into an observation group, a 6 h resveratrol intervention group and a 12 h resveratrol intervention group. Then each group was subdivided into Sham, Sham + Res, CLP and CLP + Res groups. After surgery, the survival and morphological changes in kidney tissues were observed. Serum creatinine and urea nitrogen levels, expression of GRP78, BiP, IRE1 and p65 in kidney tissues, and serum levels of TNF-α, IL-1β, IL-6 and IL-10 were investigated. The survival rate of CLP + Res group (75.00%) significantly exceeded that of the CLP group (41.67%) (P<0.05). At postoperative 12 h, resveratrol significantly decreased serum creatinine and urea nitrogen levels (P<0.05). Resveratrol evidently relieved renal tubular swelling and luminal narrowing in CLP rats, and significantly reduced the high expressions of GRP78, BiP, phosphorylated IRE1 and p65 proteins (P<0.05). P65 was mainly located in the cytoplasm of Sham, Sham + Res and CLP + Res groups, and in the nucleus of the CLP group. At postoperative 12 h, resveratrol significantly reduced serum levels TNF-α, IL-1β and IL-6 in CLP rats (P<0.05), whereas elevated that of IL-10 (P<0.05). Resveratrol significantly decreased the mortality rate of septic rats and alleviated AKI, probably by attenuating endoplasmic reticulum stress, inhibiting activation of the NF-κB pathway and mitigating the inflammatory response.

Highlights

  • Sepsis is a systemic inflammatory response syndrome caused by infection, which often occurs after severe trauma, burn and major surgery, leading to multiple organ dysfunction syndrome and even death due to uncontrollable inflammation[1]

  • Effects of resveratrol on general symptoms and tissue damages of septic rats With or without resveratrol treatment, the Sham group was free from obvious abnormalities after surgery

  • The cecal ligation and puncture (CLP) group suffered from apparent symptoms and tissue damage which were relieved in the CLP + Res group

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Summary

Introduction

Sepsis is a systemic inflammatory response syndrome caused by infection, which often occurs after severe trauma, burn and major surgery, leading to multiple organ dysfunction syndrome and even death due to uncontrollable inflammation[1]. The incidence rate of sepsis is high, and the treatment outcomes are unsatisfactory[2]. The mechanism of sepsis has been widely studied, the mortality rate is still as high as 30-70%, and is mainly responsible for the death of patients in intensive care units. The incidence rates of acute renal injury (AKI) in patients with mild, moderate and severe sepsis are 19%, 23% and 51% respectively. Early prevention and treatment of AKI have great clinical significance for reducing the mortality rate of sepsis and improving the prognosis

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