Protective Effects And Mechanisms Of Asiaticoside On The Acute Spinal Cord Injury In Rats

Objective: To study the effects of Asiaticoside , the major active component of traditional Chinese herb'Centella asiatica', on model of acute spinal cord injury in rats and its possible protective mechanisms, and to provide a theoretical basis of AS for the treatment of ASCI.Methods : Rat model of acute spinal cord injury was established by modified Allen's method. One hundred and forty rats were divided randomly into the normal group,the model group , and the groups treated with Asiaticoside (15mg/kg and 45mg/kg) and methylprednisolon (30mg/kg). At 24h, 72h, 7d, 14d and 28d after operation, motor functions of the rat hind limbs were determined by the BBB(Basso Beattie and Bresnahan), morphologic changes of spinal neurons were evaluated by HE staining, the changes of SOD activity and MDA contents in rat spinal cord were measured by xanthinoxidase method and the method of TBA separately. The COX-2 mRNA and COX-2 protein expression in rat spinal cord were detected by RT-PCR and immunohistochemistry, separately. The apoptosis of neural cells was assessed with the terminal deoxynucleotidyl transferase mediated deoxyuredine triphosphate-digoxin nick end labeling (TUNEL)method.Results: It was observed that at 24h, 72h, 7d, 14d and 28d after operation, the motor functions of the rat hind limbs about the acute spinal cord injury model group were decreased; extensive focal hemorrhage of spinal cord, large quantity of diapedesis of erythrocyte, severe interstitial edema and karyopyknosis were observed; levels of MDA were increased and activities of SOD were decreased in spinal cord tissue; TUNEL positive cells were significantly increased, as well as the protein and mRNA expression of COX-2 in the spinal cord increased,the extreme value of every index presented at 24h after operation. Treatments with AS (45 and 15mg/kg) or MP(30mg/kg)could significantly ameliorate the motor functions of the rat hind limbs, markedly decrease the elevation of MDA levels and increase the activities of SOD in spinal tissue. Meanwhile, TUNEL positive cells were significantly decreased , the damage to nerve cells were alleviated and protein and mRNA expression of COX-2 in spinal tissue induced by the acute spinal cord injury were inhibited,with statistical significance as compared with the model group at 24h, 72h, 7d, 14d and 28d after operation.Conclusion: Acute spinal cord injury can induce motoneuron damage in rats and decrease the rat hindlimbs locomotor function and induce markedly the expression of COX-2 mRNA and protein. The administration of Asiaticoside possesses neuroprotective effect on ASCI,which can improve neurological function recovery and attenuate secondary spinal cord injury.