Abstract
Objective We aimed to investigate the protective effect of s-nitrosoglutathione (SNG) pretreatment on acute kidney injury (AKI) in septic rats. Methods We constructed a rat model of sepsis by cecal ligation and puncture and observed the survival of the rats. We obtained kidney and blood samples from rats, observed the pathological damage to the kidney tissues, and evaluated kidney function and the expression levels of inflammatory factors. We also detected the expression of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the kidneys by immunohistochemistry and evaluated the apoptosis of kidney tubular epithelial cells (KTEC) by TUNEL. Results Pretreatment with SNG significantly reduced the mortality of septic rats, attenuated kidney pathological damage, and decreased the levels of serum creatinine, plasma neutrophil gelatinase-associated lipocalin, and plasma kidney injury molecule-1. Moreover, SNG pretreatment decreased the levels of TNF-α and IL-1β in serum and kidney and reduced the expressions of NO, iNOS, PGE2, and COX-2 in the kidneys. Furthermore, pretreatment with SNG significantly reduced the apoptotic rate of KTEC and decreased the levels of caspase-3 and Bax mRNA, but increased the level of Bcl-2 mRNA. Conclusion Pretreatment with SNG has a protective effect on AKI in septic rats, and the specific mechanisms are related to inhibition of inflammation, oxidation, and apoptosis.
Highlights
Acute kidney injury (AKI) is one of the common complications of patients with sepsis, and the incidence is increasing year by year [1]
We found that the mortality of rats in the cecal ligation and perforation (CLP) group was significantly increased compared with the control group, and pretreatment with SNG significantly reduced the mortality of septic rats
We found that the levels of serum creatinine (SCr), plasma neutrophil gelatinaseassociated lipocalin (pNGAL), and plasma kidney injury molecule-1 (pKIM-1) were significantly increased in the CLP group, and SNG pretreatment significantly decreased the levels of SCr, pNGAL, and pKIM-1
Summary
Acute kidney injury (AKI) is one of the common complications of patients with sepsis, and the incidence is increasing year by year [1]. Recent studies show that nearly 20 million people worldwide suffer from sepsis every year, and about 42% of the cases are complicated with AKI. The incidence increases at a rate of 1.5%-1.8% per year, with a mortality of 60% [2]. AKI is an independent prognostic risk factor for septic patients. Medical technology has made significant progress in recent years, the overall mortality is not decreased [3]. Elucidating the pathogenesis of AKI caused by sepsis is an important aspect of research in this field
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