Dexmedetomidine Ameliorates Acute Kidney Injury by Regulating Mitochondrial Dynamics Via the α2-AR/SIRT1/PGC-1α Pathway Activation in Rats

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 2024 Oct 25

PMID 39455916

Authors

Shuai Zhang

Xiujing Feng

Guiyan Yang

Haoyang Tan

Xin Cheng

Qichao Tang

Haotian Yang

Yuan Zhao

Xuanpan Ding

Siyao Li

Xinyi Dou

Junfeng Li

Huijie Kang

Xingxing Li

Yaxin Ji

Qingdian Hou

Qiuyue An

Hao Fang

Honggang Fan

Affiliations

Soon will be listed here.

Abstract

Background: Sepsis-associated acute kidney injury (AKI) is a serious complication of systemic infection with high morbidity and mortality in patients. However, no effective drugs are available for AKI treatment. Dexmedetomidine (DEX) is an alpha 2 adrenal receptor agonist with antioxidant and anti-apoptotic effects. This study aimed to investigate the therapeutic effects of DEX on sepsis-associated AKI and to elucidate the role of mitochondrial dynamics during this process.

Methods: A lipopolysaccharide (LPS)-induced AKI rat model and an NRK-52E cell model were used in the study. This study investigated the effects of DEX on sepsis-associated AKI and the molecular mechanisms using histologic assessment, biochemical analyses, ultrastructural observation, western blotting, immunofluorescence, immunohistochemistry, qRT-PCR, flow cytometry, and si-mRNA transfection.

Results: In rats, the results showed that administration of DEX protected kidney structure and function from LPS-induced septic AKI. In addition, we found that DEX upregulated the α2-AR/SIRT1/PGC-1α pathway, protected mitochondrial structure and function, and decreased oxidative stress and apoptosis compared to the LPS group. In NRK-52E cells, DEX regulated the mitochondrial dynamic balance by preventing intracellular Ca overloading and activating CaMKII.

Conclusions: DEX ameliorated septic AKI by reducing oxidative stress and apoptosis in addition to modulating mitochondrial dynamics via upregulation of the α2-AR/SIRT1/PGC-1α pathway. This is a confirmatory study about DEX pre-treatment to ameliorate septic AKI. Our research reveals a novel mechanistic molecular pathway by which DEX provides nephroprotection.

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