Study of long-term mitochondrial dysfunction and oxidative stress in a sepsis-associated encephalopathy model

Abstract

Objective To investigate the long-term mitochondrial dysfunction and oxidative stress in a sepsis-associated encephalopathy(SAE) model. Methods To initiate experimental sepsis, male Wistar rats were injected intraperitoneally with 10 mg/kg of lipopolysaccharide (LPS) dissolved in sodium chloride.Animals were evaluated by neurologic reflex scores before sacrifice and brain tissues were quickly removed at the indicated time points (0 h for control group and 12, 24, 48, 72 h post injections for SAE groups). Cerebral mitochondrial membrane potential (MMP) and reactive oxygen species(ROS) were detected by flow cytometer and superoxide dismutase(SOD), malondialdehyde(MDA), inducible nitric oxide synthase(iNOS) and nitric oxide(NO) were determined by using microplate reader. Results Deteriorated neurological reflexes were found since 12 h and recovered slowly.Cerebral MMP in 12 h SAE group was decreased significantly compared with that in the control group.MMP was decreased to the lowest level at 48 h (F=75.785, P<0.05), and partly recovered at 72 h .ROS, MDA, iNOS and NO were increased significantly at 48 h (F=111.274, 21.955, 61.076, 21.184, all P<0.05) and partly recovered at 72 h. SOD changed controversially with ROS(F=21.808, P<0.05). SOD showed strong positive linear correlations with MMP(r=0.856, P<0.05), whereas ROS, MDA, iNOS and NO showed strong negative linear correlations with MMP(r=-0.852, -0.890, -0.940, -0.794, all P<0.05). Conclusions These results suggest that long-term brain mitochondrial dysfunction of lipopolysaccharide-induced septic rat is partly affected due to an increase in oxidative stress and has a turning-point near 48 h post injections. Key words: Sepsis-associated encephalopathy; Mitochondrial dysfunction; Oxidative stress; Long-term injury