The Molecular Mechanism Of MicroRNAs Regulating Oxidative Stress Related Proteins In Hippocampal Of Rats After Traumatic Brain Injury

?Objective?This research is aimed at exploring the potential molecular mechanism of hippocampal damage by establishing moderate animal model of traumatic brain injury and detecting the expression changes of mitochondrial oxidative stress-related microRNAs and their corresponding target proteins.?Method??1?Rat models of sham groups and 1^sthour,12^thhour,1^stday,3^rdday after controlled cortical injury was established.?2?Hippocampal tissues from each groups of rats were used for histopathological examination,apoptosis detection,and MDA levels and total SOD activities to clarify the neuronal damage in the hippocampus.?3?The expression levels of mitochondrial oxidative stress-related microRNAs and their corresponding target proteins were detected via gene chip and western blotting technology.?Results??1?Obvious degeneration and necrosis of neurons was appeared in CA1 area of hippocampus after TBI,and was deteriorated over time till 3^rdd.?2?A rapid,obvious and persistent DNA damage was observed in CA3 area in hippocampal neurons after TBI.?3?TBI caused obvious damage of ROS attack to the hippocampal tissue of rats accompanied by impaired ability of antioxidant defense,showing increased levels of lipid peroxidation product MDA,and the decreased of total SOD activities;?4?The expression levels of oxidative stress-related proteins SIRT1,Fox O3 a,Trx-2 obviously decreased after TBI and then restored gradually with a nadir at 12^thhour after injury;until 1^stday after injury,similar trends were appeared in PGC-1?,but decreased again at3^rdday after injury;the expression changes of SOD2 was not statistically significant.?5?Microarray analysis and cluster analysis showed that miR-221 and miR-23 a were involved in pathophysiological process of traumatic brain injury as targets of SIRT1 and PGC-1?,respectively.?Conclusion?The expression level of miR-221 was significantly increased in hippocampus after TBI,leading to a decreased expression of its target protein SIRT1,thus the direct induction to downstream FoxO3 a,PGC-1?and Trx-2;at the same time,acetylation levels of Fox O3 a and PGC-1?was increased,similarly resulted in the inhibition of downstream Trx-2,all of this caused a weakened antioxidant capacity.In addition,miR-23a/PGC-1?may also participate in the pathophysiology of TBI as one of the regulatory mechanisms.