Effects of Corynoxine on Mitophagy in Rats with Traumatic Brain Injury
Objective:To reveal the therapeutic effect of Corynoxine(Cor)on traumatic brain injury(TBI)rats and its effect on mitophagy.Methods:Totally 80 rats were randomly divided into sham group(n=10)and modeling group(n=70).Rats in sham group only had skin incisions without modeling,while rats in modeling group established a TBI rat model.The 58 rats with successful modeling were randomly divided into model group(n=12),low dose group(n=12),middle dose group(n=12),high dose group(n=11)and inhibitor group(n=11).Rats in low,middle and high dose groups were treated with low[5 mg/(kg·d)],middle[10 mg/(kg·d)]and high[20 mg/(kg·d)]doses of corynoxine respectively.Rats in inhibitor group were treated with corynoxine[20 mg/(kg·d)]and autophagy inhibitor 3-MA[15 mg/(kg·d)].After 14 days of administration,the improved neurological deficit scoring method was used to score the neurological function,and the Morris water maze test was used to evaluate the cognitive function.The sucrose preference test and the open field test were used to evaluate the behavior.Brain tissue injury and neuronal apoptosis were evaluated by hematoxylin and eosin(HE)staining and TUNEL staining.The water content of brain tissue and the levels of oxidative stress indicators[superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)]in brain tissue were detected.The protein expressions of Bax,Bcl-2,cleaved Ccaspase-3,LC3B,p62 and Beclin-1 in brain tissue were detected by Western blotting.Results:The neurological function score,escape latency,brain water content,TUNEL positive rate,MDA level,Bax,cleaved Caspase-3,and p62 protein levels in low,middle and high dose groups were lower than those in model group,while the times of crossing the platform,sucrose preference,horizontal activity score,vertical activity score,SOD,CAT,GSH-Px,Bcl-2,LC3B-Ⅱ/LC3B-Ⅰ and Beclin-1 protein levels were higher than those in model group(P＜0.05).The neurological function score,escape latency,brain water content,TUNEL positive rate,MDA,cleaved Caspase-3 and p62 protein levels in inhibitor group were higher than those in high dose group,while the platform crossing times,sucrose preference,horizontal activity fraction,vertical activity fraction,SOD,CAT,GSH-Px,Bel-2 Bcl-2,LC3B-Ⅱ/LC3B-Ⅰ and Beclin-1 protein levels in the inhibitor group were lower than those in high dose group(P＜0.05).Conclusion:Corynoxine can effectively reduce the secondary injury after TBI,inhibit neuronal apoptosis and oxidative stress,and its mechanism may be related to the activation of mitophagy.
万方数据
维普
