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Received Aug 27, 2017; Revised Nov 21, 2017; Accepted Dec 4, 2017
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1. Introduction
AKI is a clinical syndrome caused by various factors and characterized by a rapid decline in renal function. Sepsis is the most common cause of AKI (40%–50%) in critically ill patients, and the mortality of SA-AKI is as high as 70% [1, 2]. The pathogenesis of SA-AKI is complicated, including inflammation, coagulation cascade activation, oxidative stress, microcirculatory disturbance, renal hypoperfusion, and renal venous congestion [3, 4]. Despite the growing understanding of the pathophysiological mechanisms of AKI, the development of pharmacological treatments for AKI shows little progress.
LPS is a normal component of cell wall of most Gram-negative bacteria, which can trigger cytokine synthesis, secretion, and a subsequent inflammatory process. Previous studies have demonstrated that LPS is one of the most important causes of sepsis and is involved in the pathogenesis of SA-AKI, which may lead to “cytokine storm,” intensified oxidative stress, low blood pressure, renal hypoperfusion, and finally a gradual decline in renal function [5–7]. Toll-like receptors (TLRs) are the most important pattern-recognition receptors and play a key role in innate immunity. The major receptor for LPS is TLR4 [8, 9], which is activated after LPS binding, and induces downstream signaling cascades as well as expression of inflammatory cytokines [10]. Nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is one of the most important members of the Nod-like receptor (NLR) family, including NLRP3, the adaptor protein ASC, and a cysteine protease caspase-1. Abderrazak et al. [11] have found that NLRP3 inflammasome participated in the inflammatory process and may be critical for the development of sepsis and AKI. Activation of NLRP3 inflammasome could promote the maturation and release of proinflammatory cytokines IL-1β and IL-18. Another study found that NLRP3 expression induced by LPS was dose- and time-dependent, but it failed to induce NLRP3 expression in cells in the absence of TLR4 [12].
H2S was considered to be toxic for a long time until endogenous H2S was discovered in the rat brain [13]. H2S is mainly...