Study On N6 Promotes Spinal Cord Injury Repair In Rats By Adjusting The Endoplasmic Reticulum Stress

[Objective]:Spinal cord injury(SCI)is a/the serious central nervous system trauma,which can lead to severe nerve dysfunctions.The main performance of SCI is the obstacle of motor,sensory and reflection under the injury plane of body.SCI can lead to disability or even death of patients,which could result in heavy economic burden to society.Endoplasmic reticulum stress(ERS)is associated with many diseases of the nervous system.Recent studies have pointed out that ERS played an important role in lots of nervous diseases,even in the pathological process of spinal cord injury.GRP78 and CHOP were the key proteins of ERS.Cocktail neuroprotectant N6(including dexamethasone,GM1,neurotrophic factor,etc)is a kind of drug for SCI treatment based on clinical experience and animal experiments.Our early studies have shown that N6 can reduce the lipid peroxidation level and neurocyte apoptosis of SCI rat.We investigated the expression of GRP78 and CHOP in spinal cord tissues as well as the recovery of motor function,to explore the protective mechanisms of N6 by mading an animal model of SCI with Sprague-Dawley rats.This research will provide theoretical basis for N6 in improving the formula and the using in clinic.[Methods]:60 SD rats were randomly divided into 5 groups:sham group(Sham),spinal cord injury group(SCI),intraperitoneal injection of methylprednisolone group(MP-a),intrathecal injection of methylprednisolone group(MP-b)and intrathecal injection of cocktail neuroprotectant N6 group(Cocktail).Each group had 12 rats.Using the NYU impactor to establish the rat model of acute SCI,10 min later,treatment groups were given corresponding drug treatment.72 hours after treatment,we detected the expression level of GRP78 and CHOP using western-blot and CHOP immunofluorescence staining.Basso-Beattie-Bresnahan(BBB)score testing was employed to evaluate the remaining rats' locomotor function of hindlimbs on1,7,14,21,28 d after operation.All remaining rats were sacrificed on 28 d after operation.Luxol Fast Blue(LFB)staining was used to observe the regeneration of myelin sheath.[Results]:Compared with group SCI,MP-a and MP-b,the expression of CHOP of group Cocktail was significantly lower(P < 0.05)and the GRP78 level was higher(P < 0.05);The BBB score of group Cocktail was significantly higher in 14 d,21d and 28d(P <0.05);The area of myelin sheath of group Cocktail was bigger(P < 0.05).No Statistical difference of the GRP78 &CHOP expression quantity and BBB socres were founded between MP-a and MP-b group.[Conclusion] : Cocktail neuroprotectant N6 intrathecal injection,can increase the expression of GRP78,reduce the expression of CHOP,adjust the level of ERS,to promote the recovery of hindlimb motor function and myelin regeneration of SCI rats.