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Abstract
Objective: The aim of the study was to determine whether hepatocyte mitochondrial injury instigates severe shock and to explore effective therapy.
Methods: Wistar rats were randomly divided into five groups: Control (sham) group, shock + normal saline, shock + cyclosporine A, shock + resveratrol (Res) and shock + polydatin (PD) group. Mitochondrial morphology and function in hepatocytes following treatment were determined.
Results: Hepatocytes following severe shock exhibited mitochondrial dysfunction characterized with opening of mitochondrial permeability transition pores, mitochondrial swelling, decreased mitochondrial membrane potential (ΔΨm) and reduced ATP levels. Moreover, severe shock induced oxidative stress with increased lipid peroxidation and reactive oxygen species, decreased SOD2 (Superoxide Dismutase 2) and GSH/GSSG, which resulted in increased lysosomal membrane permeabilization and hepatocyte mitochondrial injury. Additionally, Res and PD restored decreased deacetylase sirtuin1 activity and protein expression in liver tissue following severe shock, suppressed oxidative stress-induced lysosomal unstability and mitochondrial injury by increasing the protein expression of SOD2, and thereby contributed to the prevention of hepatocyte mitochondria dysfunction and liver injury.
Conclusions: PD effectively preserved hepatocytes from mitochondrial injury via SIRT1-SOD2 pathway and may be a new approach to treatment of irreversible shock.
Declaration of interest
This work was supported by National Natural Science Foundation of China [No.30672179, 30971202, 81200234], National Science and Technology Major Project [2011ZX09101-002-08]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.