scholarly journals Ulinastatin improves renal microcirculation by protecting expression of VE-cadherin and inhibiting autophagy in a septic rat model

2021 ◽  
Author(s):  
Tian Li ◽  
Xiao-jun Ji ◽  
Jing-feng Liu ◽  
Xin-jie Guo ◽  
Ran Pan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Rat Model ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Male Adult ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Renal Microcirculation ◽  
Cell Stability

Abstract Background: Increased permeability of the renal capillary is a common consequence of sepsis-associated acute kidney injury. Vascular endothelial (VE)-cadherin is a strictly endothelial-specific adhesion molecule that can control the permeability of the blood vessel wall, and autophagy plays an important role in maintaining cell stability. Ulinastatin, a urinary trypsin inhibitor, attenuates the systemic inflammatory response and visceral vasopermeability. However, it is uncertain whether ulinastatin can improve renal microcirculation by acting on the adhesion junction. Methods: We obserned the effect of Ulinastatin in the septic rat model by using contrast-enhanced ultrasonography (CEUS) to evaluate perfusion of the renal cortex and medulla. Male adult Sprague-Dawley rats were subjected to cecal ligation and puncture and divided into the sham, sepsis, and ulinastatin groups. Ulinastatin (50 000 U/kg) was injected into the tail vein 1 hour after the operation. At 24 hours postoperatively, CEUS was performed to evaluate the renal microcirculation blood flow and microcirculation perfusion. Histological staining was used to evaluate kidney injury scores. Western blotting was used to assess the expression of VE-cadherin and LC3II, peripheral serum cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α levels), renal function (creatinine, urea nitrogen, and S-thrombomodulin level), and the urine neutrophil gelatinase-associated lipocalin level. Results: Compared with sham group, ulinastatin reduced the inflammatory response, maintained the expression of VE-cadherin, inhibited autophagy, and meliorated cortical and medullary perfusion.Conclusions: Ulinastatin effectively protects the adhesion junction and helps to ameliorate the perfusion of kidney capillaries during sepsis by inhibiting autophagy and the expression of inflammatory factors.

scholarly journals Ulinastatin improves renal microcirculation by protecting endothelial cells and inhibiting autophagy in a septic rat model

2022 ◽  
Author(s):  
Tian Li ◽  
Xiaojun Ji ◽  
Jingfeng Liu ◽  
Xinjie Guo ◽  
Ran Pang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Rat Model ◽  
Cecal Ligation ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sprague Dawley ◽  
Male Adult ◽  
Renal Microcirculation

Introduction: Increased permeability of the renal capillaries is a common consequence of sepsis-associated acute kidney injury. Vascular endothelial (VE)-cadherin is a strictly endothelial-specific adhesion molecule that can control the permeability of the blood vessel wall. Additionally, autophagy plays an important role in maintaining cell stability. Ulinastatin, a urinary trypsin inhibitor, attenuates the systemic inflammatory response and visceral vasopermeability. However, it is uncertain whether ulinastatin can improve renal microcirculation by acting on the endothelial adhesion junction. Methods: We observed the effect of ulinastatin in a septic rat model using contrast-enhanced ultrasonography (CEUS) to evaluate the perfusion of the renal cortex and medulla. Male adult Sprague-Dawley rats were subjected to cecal ligation and puncture and divided into the sham, sepsis, and ulinastatin groups. Ulinastatin (50,000 U/kg) was injected into the tail vein immediately after the operation. The CEUS was performed to evaluate the renal microcirculation perfusion at 3, 6, 12, and 24 hours after the operation. Histological staining was used to evaluate kidney injury scores. Western blot (WB) was used to quantify the expression of VE-cadherin, LC3II, and inflammatory factors [interleukin -1β (IL-1β), interleukin -6 (IL-6), and tumor necrosis factor-α (TNF-α)] in kidney tissue, and enzyme-linked immunosorbent assay (ELISA) detected serum inflammatory factors and kidney function and early kidney injury biomarker levels. Results: Compared with the sham group, ulinastatin reduced the inflammatory response, inhibited autophagy, maintained the expression of VE-cadherin, and meliorated cortical and medullary perfusion. Conclusion: Ulinastatin effectively protects the adhesion junction and helps ameliorate the perfusion of kidney capillaries during sepsis by the inhibition of autophagy and the expression of inflammatory factors.

Protection of resveratrol on acute kidney injury in septic rats

2016 ◽  
Vol 36 (10) ◽  
pp. 1015-1022 ◽  
Author(s):  
Y Gan ◽  
S Tao ◽  
D Cao ◽  
H Xie ◽  
Q Zeng
Keyword(s):  
Acute Kidney Injury ◽  
Survival Rate ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Sham Operation ◽  
Serum Cystatin C ◽  
Injury Index ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Kidney Injury Molecule 1

Aim: The aim of the study is to investigate protective effect of resveratrol (Res) on acute kidney injury (AKI) in sepsis. Methods: Rats in sham group received sham operation; in sham + Res received sham operation and Res (3 mg/kg); in cecal ligation and puncture (CLP) established as sepsis; in CLP + Res (3 mg/kg) with sepsis and Res (3 mg/kg); and in CLP + Res (10 mg/kg) with sepsis and Res (10 mg/kg). Survival rate, serum indexes, inflammatory factors, NF-κB-P65, and SIRT1 were detected. Lipopolysaccharide (LPS) mesangial cell was with Res and SIRT1 silencing. Results: (1) Res intervention improved survival rate of CLP rat. (2) Compared to sham, serum creatinine, blood urine nitrogen, serum cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, tumor necrosis factor-α, interleukin-1β, IL-6, and renal injury index increased in CLP group, while decreased in CLP + Res (3 mg/kg) and CLP + Res (10 mg/kg), significantly, as dose-dependent ( p < 0.05). (3) With Res, NF-κB-P65 and de-acetylated SIRT1 decreased, while SIRT1 and de-acetylated Nuclear factor kB-p65 9 NF-κB-P65) increased, significantly ( p < 0.05). (4) SIRT1 and de-acetylated NF-κB-P65 decreased in LPS cells, while SIRT1 increased after Res intervention, significantly ( p < 0.05). After silencing SIRT1, de-acetylated NF-κB-P65 increased, significantly ( p < 0.05). Conclusions: Res increases the survival rate of septic rats by inhibiting inflammatory factors to ease AKI and promotes NF-κB-P65 de-acetylation by upregulating SIRT1.

scholarly journals Pretreatment with S-Nitrosoglutathione Attenuates Septic Acute Kidney Injury in Rats by Inhibiting Inflammation, Oxidation, and Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Heng Fan ◽  
Jian-wei Le ◽  
Min Sun ◽  
Jian-hua Zhu
Keyword(s):  
Acute Kidney Injury ◽  
Protective Effect ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Septic Acute Kidney Injury ◽  
Cox 2 ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

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.

scholarly journals Ventilator-induced lung injury increases expression of endothelial inflammatory mediators in the kidney

2017 ◽  
Vol 312 (4) ◽  
pp. F654-F660 ◽  
Author(s):  
Mark Hepokoski ◽  
Joshua A. Englert ◽  
Rebecca M. Baron ◽  
Laura E. Crotty-Alexander ◽  
Mark M. Fuster ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Inflammatory Mediators ◽  
Cecal Ligation ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Ventilator Induced Lung Injury ◽  
Angiopoietin 2 ◽  
Neutrophil Gelatinase

In critical illness, such as sepsis or the acute respiratory distress syndrome, acute kidney injury (AKI) is common and associated with increased morbidity and mortality. Mechanical ventilation in critical illnesses is also a risk factor for AKI, but it is potentially modifiable. Injurious ventilation strategies may lead to the systemic release of inflammatory mediators from the lung due to ventilator induced lung injury (VILI). The systemic consequences of VILI are difficult to differentiate clinically from other systemic inflammatory syndromes, such as sepsis. The purpose of this study was to identify unique changes in the expression of inflammatory mediators in kidney tissue in response to VILI compared with systemic sepsis to gain insight into direct effects of VILI on the kidney. Four groups of mice were compared—mice with sepsis from cecal ligation and puncture (CLP), mice subjected to injurious mechanical ventilation with high tidal volumes (VILI), mice exposed to CLP followed by VILI (CLP+VILI), and sham controls. Protein expression of common inflammatory mediators in kidneys was analyzed using a proteome array and confirmed by Western blot analysis or ELISA. VEGF and VCAM-1 were found to be significantly elevated in kidneys from VILI mice compared with sham and CLP. Angiopoietin-2 was significantly increased in CLP+VILI compared with CLP alone and was also correlated with higher levels of AKI biomarker, neutrophil gelatinase-associated lipocalin. These results suggest that VILI alters the renal expression of VEGF, VCAM-1, and angiopoietin-2, and these proteins warrant further investigation as potential biomarkers and therapeutic targets.

scholarly journals INT-777 Improves Cognitive Impairment after Sepsis by Attenuating Neuroinflammation Through the TGR5/cAMP/PKA/CREB Signaling Axis in Rats

2020 ◽  
Author(s):  
Peng Jin ◽  
Shuixiang Deng ◽  
Mi Tian ◽  
Pengju Wei ◽  
Yao Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Survival Rate ◽  
Cell Activation ◽  
Cecal Ligation ◽  
Clinical Score ◽  
Inflammatory Factors ◽  
Experimental Sepsis ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Sepsis Survivors

Abstract Background: Sepsis survivors are left with significant cognitive and behavioral impairments after discharge, but research on the relevant mechanisms and interventions remains lacking. TGR5 plays a neuroprotective role in many neurologic disease models through different mechanisms. To date, no studies have assessed the effects of TGR5 on neuroinflammation or cognitive or behavioral changes in sepsis models.Methods: A total of 267 eight-week-old male Sprague-Dawley rats were used in this study. Sepsis was induced by cecal ligation and puncture (CLP). All animals received volume resuscitation. The rats were given TGR5 CRISPR oligonucleotide intracerebroventricularly 48 hours before CLP surgery. INT-777 was administered intranasally 1 hour after CLP, and the cAMP inhibitor SQ22536 was administered intracerebroventricularly 1 hour after CLP. Survival rate, bodyweight change, clinical score, neurobehavioral tests, western blot, and immunofluorescence staining were performed. The cognitive function of rats was measured by Morris water maze during 15-20 days after CLP.Results: The expression of TGR5 in the rat hippocampus was upregulated and peaked at 3 days after CLP. The survival rate of rats after CLP was less than 50%, and the growth rate in terms of weight was significantly decreased, while these changes were not improved by INT-777 treatment. However, INT-777 treatment reduced the clinical scores of rats at 24 hours after CLP. On day 15 and later, the surviving mice completed a series of behavioral tests. CLP rats showed spatial and memory deficits and anxiety-like behaviors, and INT-777 treatment significantly improved these effects. Mechanistically, immunofluorescence analysis showed that INT-777 treatment reduced the number of microglia in the hippocampus, neutrophil infiltration and the expression of inflammatory factors after CLP in rats. Moreover, INT-777 treatment significantly increased the expression of TGR5, cAMP, p-PKA, and p-CREB and downregulated the expression of IL-1β, IL-6 and TNF-α. CRISPR-mediated TGR5 knockdown and SQ22536 treatment abolished the neuroprotective effects of TGR5 activation after CLP.Conclusion: This study demonstrates that INT-777 treatment reduced neuroinflammation and microglial cell activation, and then improved cognitive impairment in the experimental sepsis rats. TGR5 has translational potential as a therapeutic target to improve neurological outcomes in sepsis survivors.

scholarly journals BETTERMENT OF DICLOFENAC-INDUCED NEPHROTOXICITY BY PENTOXIFYLLINE THROUGH MODULATION OF INFLAMMATORY BIOMARKERS

2019 ◽  
pp. 433-437
Author(s):  
HAYDER M. AL-KURAISHY ◽  
ALI I. AL-GAREEB ◽  
NAWAR RAAD HUSSIEN
Keyword(s):  
Tissue Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Inflammatory Biomarkers ◽  
Renal Diseases ◽  
Distilled Water ◽  
Sprague Dawley ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Group 2 ◽  
Neutrophil Gelatinase

Objectives: Diclofenac-induced nephrotoxicity is caused by oxidative stress which leads to lipid peroxidation and formation of free radicals. Pentoxifylline can ameliorates renal tissue injury by its anti-inflammatory, antifibrotic, and antioxidant effects, so it mitigates the progression of renal diseases. Therefore, the aim of this study was to evaluate the nephroprotective effects of pentoxifylline on diclofenac-induced nephrotoxicity in rats. Methods: A total of 30 male Sprague-Dawley rats were allocated into three groups, Group 1 (n=10): Rats treated with distilled water 5 ml/kg plus normal saline 5 ml/kg for 12 days, Group 2 (n=10): Rats treated with distilled water 5 ml/kg plus diclofenac 15 mg/kg for 12 days, and Group 3 (n=10): Rats treated with pentoxifylline 100 mg/kg plus diclofenac 15 mg/kg for 12 days. Blood urea, creatinine, malondialdehyde (MDA), superoxide dismutase (SOD-1), glutathione reductase (GSH), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecules (KIM-1) vitronectin (VTN), integrin (ITG) , interleukin-18 (IL-18) and cystatin-C were used to measure the severity of nephrotoxicity. Results: Diclofenac-induced nephrotoxicity led to significant elevation in blood urea, serum creatinine, MDA, IL-18, KIM-1, NGAL, serum ITG, and VTN with decrease of SOD-1 and GSH sera levels p<0.05. Treatment with pentoxifylline showed no significant effect on all biomarker levels compared to diclofenac group except on serum level KIM-1 and serum VTN, p<0.05. Conclusion: Pentoxifylline produced significant nephroprotective effect on diclofenac-induced nephrotoxicity through modulation of inflammatory biomarkers.

scholarly journals Lack of synergistic nephrotoxicity between vancomycin and piperacillin/tazobactam in a rat model and a confirmatory cellular model

2020 ◽  
Vol 75 (5) ◽  
pp. 1228-1236 ◽  
Author(s):  
Gwendolyn M Pais ◽  
Jiajun Liu ◽  
Sean N Avedissian ◽  
Danielle Hiner ◽  
Theodoros Xanthos ◽  
...  
Keyword(s):  
Rat Model ◽  
Kidney Injury ◽  
Cellular Injury ◽  
Cellular Model ◽  
Sprague Dawley ◽  
Injury Score ◽  
Sprague Dawley Rats ◽  
High Doses ◽  
Vancomycin Group ◽  
Synergistic Toxicity

Abstract Background Vancomycin and piperacillin/tazobactam are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated synergistic toxicity, only that serum creatinine increases. Objectives To clarify the potential for synergistic toxicity between vancomycin, piperacillin/tazobactam and vancomycin + piperacillin/tazobactam treatments by quantifying kidney injury in a translational rat model of AKI and using cell studies. Methods (i) Male Sprague–Dawley rats (n = 32) received saline, vancomycin 150 mg/kg/day intravenously, piperacillin/tazobactam 1400 mg/kg/day intraperitoneally or vancomycin + piperacillin/tazobactam for 3 days. Urinary biomarkers and histopathology were analysed. (ii) Cellular injury was assessed in NRK-52E cells using alamarBlue®. Results Urinary output increased from Day −1 to Day 1 with vancomycin but only after Day 2 for vancomycin + piperacillin/tazobactam-treated rats. Plasma creatinine was elevated from baseline with vancomycin by Day 2 and only by Day 4 for vancomycin + piperacillin/tazobactam. Urinary KIM-1 and clusterin were increased with vancomycin from Day 1 versus controls (P &lt; 0.001) and only on Day 3 with vancomycin + piperacillin/tazobactam (P &lt; 0.001, KIM-1; P &lt; 0.05, clusterin). The histopathology injury score was elevated only in the vancomycin group when compared with piperacillin/tazobactam as a control (P = 0.04) and generally not so with vancomycin + piperacillin/tazobactam. In NRK-52E cells, vancomycin induced cell death with high doses (IC50 48.76 mg/mL) but piperacillin/tazobactam did not, and vancomycin + piperacillin/tazobactam was similar to vancomycin. Conclusions All groups treated with vancomycin demonstrated AKI; however, vancomycin + piperacillin/tazobactam was not worse than vancomycin. Histopathology suggested that piperacillin/tazobactam did not worsen vancomycin-induced AKI and may even be protective.

scholarly journals Does Resveratrol Play a Role in Decreasing the Inflammation Associated with Contrast Induced Nephropathy in Rat Model?

2019 ◽  
Vol 8 (2) ◽  
pp. 147 ◽  
Author(s):  
Yi-Hsin Chen ◽  
Yun-Ching Fu ◽  
Ming-Ju Wu
Keyword(s):  
Single Dose ◽  
Contrast Media ◽  
Rat Model ◽  
Kidney Tissue ◽  
The Other ◽  
Control Group ◽  
Sprague Dawley ◽  
Contrast Induced Nephropathy ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Media Group

Contrast is widely used in invasive image examinations such as computed tomography (CT) and angiography; however, the risk of contrast-induced nephropathy (CIN) is high. The aim of this study was to investigate the protective effect of resveratrol in a rat model of CIN. Sprague-Dawley rats were divided into four groups: the control group (0.9% saline infusion only); resveratrol group (RSV, resveratrol, 30 mg/kg); contrast media group (CIN); and resveratrol + contrast media group (RCIN, resveratrol 30 mg/kg 60 min before CIN). CIN was induced via an intravenous injection of a single dose of indomethacin (10 mg/kg), one dose of N-nitro-L-arginine methyl ester (10 mg/kg), and a single dose of contrast medium iopromide (2 g/kg). Blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were higher in the CIN group compared to the other groups. Histopathological tubule injury scores were also higher in the CIN group compared to the other groups (p < 0.01). NLPR3 in kidney tissue were higher in the CIN group compared to the other groups; however, these results were improved by resveratrol in the RCIN group compared with the CIN group. The expressions of IL-1β and the percentage of apoptotic cells were higher in the CIN group than in the control and RSV groups, but they were lower in the RCIN group than in the CIN group. The expression of cleaved caspase-3 was higher in the CIN group than in the control and RSV groups, but lower in the RCIN group than in the CIN group. Resveratrol treatment attenuated both injury processes and apoptosis and inhibited the inflammasome pathway in this rat CIN model.

scholarly journals Experimental study on the regulation of the cholinergic pathway in renal macrophages by microRNA-132 to alleviate inflammatory response

2018 ◽  
Vol 16 (1) ◽  
pp. 176-183
Author(s):  
Ming Wu ◽  
Nana Li ◽  
Ji Xu ◽  
Lefeng Wu ◽  
Mingli Li ◽  
...  
Keyword(s):  
Cell Culture ◽  
Inflammatory Response ◽  
Hemorrhagic Shock ◽  
Culture System ◽  
Kidney Injury ◽  
Glucose Deprivation ◽  
Stable Expression ◽  
Inflammatory Factors ◽  
Cell Culture System ◽  
Expression Levels

AbstractMicroRNA-132 (miR-132) is correlated with inflammatory response regulation, although its effect on acute kidney injury to provide protection against hemorrhagic shock remains currently unknown. AChE in macrophages of the kidney subjected under hemorrhagic shock is presumed to be regulated by miR-132 after its transcription to alleviate the inflammatory response accordingly. Antagonists such as acetylcholine (Ach) (concentration 10−4mol/L) and galanthamine (Gal) (concentration 10μmol/L) were added into separate groups 1 hour after the macrophages in the kidney were isolated and cultured to induce injury under oxygen and glucose deprivation (OGD) and then cultured for 24 hours. To analyze the effect of miR-132, we placed the renal epithelial cells transfected with miR-132 plasmids with stable expression over the renal macrophages to create a double cell culture system. The expression levels of inflammatory factors and apoptosis under OGD were significantly higher in renal macrophages than in other experimental groups. Moreover, the expression of miR-132 in macrophages of the double cell culture system showing stable expression of miR-132 increased, whereas that of several inflammatory factors was significantly inhibited. The expression levels of AChE mRNA and protein in the macrophages significantly decreased. The cholinergic antiinflammatory pathway in renal macrophages is regulated by miR-132 via inhibition of the hydrolytic activity of cholinesterase to alleviate inflammatory response, which may play a role in the prevention and treatment of kidney injury caused by hemorrhagic shock.

scholarly journals SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Siqi Xu ◽  
Youguang Gao ◽  
Qin Zhang ◽  
Siwei Wei ◽  
Zhongqing Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Survival Time ◽  
Rat Model ◽  
Cecal Ligation ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Multiple Organ ◽  
Organ Systems

Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI.

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