Effect Of Atorvastatin On Autophagy And Recovery Of Motor Nerve Function After Spinal Cord Injury In Rats

ObjectiveTo investigate the effects of atorvastatin on the autophagy activity of neuralcells and neurological function recovery after spinal cord injury.MethodsThe healthy adult male SD rats were randomly divided into three groups:atorvastatin group(Ato,n = 22),saline group(Saline,n = 22)and sham group(Sham,n = 22,laminectomy only).Atorvastatin(5 mg / kg)and normal saline as control were injected intraperitoneally immediately after spinal cord injury established by Allen's method.The same dose of atorvastatin and control solvent were injected at the same time point on the first day and the second day after spinal cord injury.The motor function of the hind limbs in different treatment groups were observed by the BBB score at 1,3,7,14,21,28,35 and42 days after injury.The expressions of autophagy marker proteins(Beclin-1and LC3-B)and apoptosis-related proteins(caspase-9 and caspase-3)were detected by western blot on day 7,and RT-PCR was used to detected the expression of gene level of the autophagy markers(Beclin-1 and LC3-B).The changes of apoptotic in moto neurons of the spinal cord anterior horn after spinal cord injury were observed by TUNEL staining.ResultsAt 14 days and subsequent point in time after spinal cord injury,atorvastatin significantly promoted the recovery of hind limb motor function(p<0.05).Western blot and RT-PCR results showed that autophagy marked proteins: Beclin-1 and LC3-B protein levels and gene levels were significantly up-regulated by atorvastatin on 7 days after spinal cord injury,which meant thatatorvastatin activated nerve cell autophagy activity after spinal cord injury.In addition,Western blot results showed that the expression of caspase-9 and caspase-3 were significantly inhibited by atorvastatin,and similarly,TUNEL staining showed that atorvastatin significantly inhibited apoptosis of spinal cord anterior horn motor neurons after spinal cord injury.ConclusionsWe investigated for the first time of the correlation between atorvastatin and autophagy after spinal cord injury.The study demonstrated that atorvastatin significantly increased the autophagy activity of neurons,inhibited neuronal apoptosis,promoted function recovery after spinal cord injury,which with neuroprotective effect.