Effect of olipoprotein E mimetic peptide on neuronal apoptosis and autophagy after traumatic brain injury / 中华神经医学杂志

ABSTRACT

Objective To investigate the effect ofolipoprotein E (ApoE) mimetic peptide on neural apoptosis and autophagy and their mechanisms in mice after traumatic brain injury (TBI).Methods A total of 40 health adult male C57BL/6J mice were randomly divided into sham-operated group,TBI+normal saline (NS) group,TBI+COG1410 (1 mg) group and TBI+COG1410 (2 mg) group (n=10).The TBI models of moderate mice were constructed by controlled cortex impact (CCI) devices in the later three groups and mice in the sham-operated group were performed bone window operning only.Thirty min after model making,COG1410 treatment was given by intravenous injection of COGl410 via the tail vein at a dose of 1 mg/kg.d or 2 mg/kg.d.Mice in sham-operated group and TBI+NS group were injected with equal sterile NS instead.Neurological functions were tested 3 d after TBI by rolling-bar test and modified neurological severity scale (mNSS).Neural apoptosis was analyzed by TUNEL and autophagy protein LC3 expression in the neurons of cortex around the lesion focus was detected by immunofluorescence.Western blotting was employed to detect the expressions of apoptosis-related proteins (Bax,Bcl-2 and Caspase-3) and autophagy proteins (Beclin-1,LC3-Ⅰ and LC3-Ⅱ),and changes of Akt,mTOR,phosphorylated-(p-) Akt,p-mTOR levels.Results As compared with those in the sham-operated group,significantly shortened rotarod latency,significantly increased mNSS scores,significantly increased Bax and Caspase-3 protein expressions,significantly decreased Bcl-2,significantly increased Beclin-1 and LC3-Ⅱ protein expressions and number of TUNEL postive neurons,and statistically increased p-Akt and p-mTOR levels in the TBI+NS group were noted (P＜0.05).As compared with those in the TBI+NS group,significantly increased rotarod latency,significantly decreased mNSS scores,significantly decreased Bax and Caspase-3 protein expressions,significantly increased Bcl-2,significantly decreased Beclin-1 and LC3-Ⅱ protein expressions and number of TUNEL postive neurons,and statistically increased p-Akt and p-mTOR levels in the TBI+COG1410 (1 mg) group and TBI+COG 1410 (2 mg) group were noted (P＜0.05).As compared with those in the TBI+COG 1410 (1 mg) group,significantly increased rotarod latency,significantly decreased mNSS scores,significantly decreased Bax and Caspase-3 protein expressions,significantly increased Bcl-2 expression,significantly decreased Beclin-1 and LC3-Ⅱ protein expressions and number of TUNEL postive neurons,and statistically increased p-Akt and p-mTOR levels in the TBI+COG1410 (2 mg) group were noted (P＜0.05).Conclusion ApoE peptide is effective in reducing the excessive neuronal apoptosis and neurological dysfunctions caused by excessive neuronal autophagy after TBI,which is associated with the modulation of Akt/mTOR related pathway.