Related Experiment Video
Updated: Oct 29, 2025
Standardized Colon Ascendens Stent Peritonitis in Rats - a Simple, Feasible Animal Model to Induce Septic Acute Kidney Injury
Published on: February 15, 2022
Sirtuin 3 deficiency promotes acute kidney injury induced by sepsis via mitochondrial dysfunction and apoptosis
Heng Fan1, Jian-Wei Le1, Min Sun1
1Department of Intensive Care Unit, Ningbo First Hospital, Ningbo, Zhejiang Province, P.R China.
Objectives:
To explore the regulation mechanism of Sirtuin 3 (SIRT3) on the mitochondrial function and apoptosis of acute kidney injury (AKI) in septic mice.
Materials And Methods:
The sepsis-induced AKI model was constructed in the wild-type and SIRT3 knockout (KO) mice, and the levels of serum creatinine (Scr) and plasma kidney injury molecule 1 (pKIM-1) in mice were detected by ELISA. The mitochondrial damage of kidney tubular epithelial cells (KTEC) was observed by electron microscopy, the apoptosis of KTEC was detected by TUNEL assay, and the mRNA levels of SIRT3, Bax, Caspase-3, and Bcl-2 were detected by RT-qPCR.
Results:
SIRT3 KO caused increased expression of Scr, pKIM-1, and inducible nitric oxide synthase protein in the kidneys of septic mice, and decreased the levels of superoxide dismutase, catalase, and mitochondrial complex enzymes I/II/III/IV. SIRT3 deficiency exacerbated histopathological and mitochondrial damage to the proximal tubules of the kidney. In addition, SIRT3 KO resulted in a significantly increased apoptosis of KTEC, increased the mRNA levels of Bax and Caspase-3, and decreased the mRNA levels of Bcl-2.
Conclusion:
Our study suggests that SIRT3 deficiency promotes sepsis-induced AKI via increasing oxidative stress, mitochondrial dysfunction, and inducing apoptosis.
Insights
Sirtuin 3 (SIRT3) deficiency worsens sepsis-induced acute kidney injury (AKI) by increasing oxidative stress, mitochondrial dysfunction, and apoptosis in kidney cells. Restoring SIRT3 may protect against AKI.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Sepsis-induced acute kidney injury (AKI) is a critical condition with significant mortality.
- Mitochondrial dysfunction and apoptosis play key roles in the pathogenesis of AKI.
- Sirtuin 3 (SIRT3) is a mitochondrial deacetylase implicated in cellular stress responses.
Purpose of the Study:
- To investigate the regulatory role of Sirtuin 3 (SIRT3) in mitochondrial function and apoptosis during sepsis-induced AKI.
- To elucidate the mechanism by which SIRT3 influences kidney injury in a mouse model of sepsis.
Main Methods:
- Established a sepsis-induced AKI model in wild-type and SIRT3 knockout (KO) mice.
- Assessed kidney injury markers (serum creatinine, plasma kidney injury molecule 1) using ELISA.
- Evaluated mitochondrial damage via electron microscopy and apoptosis using TUNEL assay.
- Quantified mRNA levels of key apoptosis-related genes (Bax, Caspase-3, Bcl-2) and SIRT3 using RT-qPCR.
Main Results:
- SIRT3 deficiency in septic mice led to elevated serum creatinine and plasma kidney injury molecule 1.
- SIRT3 knockout mice exhibited increased oxidative stress, impaired mitochondrial enzyme activity, and exacerbated kidney histopathology.
- SIRT3 deficiency significantly increased kidney tubular epithelial cell apoptosis, with altered expression of Bax, Caspase-3, and Bcl-2.
Conclusions:
- SIRT3 deficiency exacerbates sepsis-induced AKI by promoting oxidative stress and mitochondrial dysfunction.
- SIRT3 plays a protective role against kidney injury during sepsis by inhibiting apoptosis.
- Targeting SIRT3 may offer a therapeutic strategy for managing sepsis-induced AKI.
Related Concept Videos
01:22Acute Kidney Injury I: Introduction
01:29Acute Kidney Injury II: Pathophysiology
01:29Acute Kidney Injury III: Clinical Manifestations
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:24Nephrotic Syndrome I : Introduction
01:20Acute Kidney Injury V: Interprofessional Care