Experiment Study Of Combined Administration Of Nafamostat And Methylprednisolone On Repairing Spinal Cord Injury

ObjectiveTo observe the role of treatment to spinal cord injury (SCI) by conbined administration of Nafamostat and Methylprednisolone in wistar rats with spinal cord injury.Methods80female Wistar rats, weighing (240±20) g were randomly divided into4groups as follows (each group number is20):control group (group Ⅰ) received normal saline10mg/kg daily by intraperitoneal injuections, Nafamostat group (group Ⅱ) received Nafamostat10mg/kg daily by intraperitoneal injections, Methylprednisolone group (groupⅢ) received Methylprednisolone30mg/kg once8h after spinal cord injury intravenous injection, conbined group (group Ⅳ) received both Nafamostat10mg/kg daily by intraperitoneal injuections and Methylprednisolone30mg/kg once8h after spinal cord injury intravenous injection. The injured epicenter of spinal cord is made by IMPACTOR MODEL-Ⅱ weight drop apparatus. Eight weeks later, all rats were killed and poured with4%polyoxymethylene. The spinal cords were taken out and subsequently postfixed in the PFA. Paraffin embedded tissues were made and the slice of spinal cord were cut into5μm thick. The recoveries of hindlimb were observed using Basso-Beattie-Bresnahan locomotor scoring scale at the time of24h,3d,5d,1w,2,3w,4w,5w,6w,7w,8w post injury. The spinal cord tissue was taken to observe the expression of GFAP, NF-200at the time of the8w after SCI, and to detect the apoptosis and myelin axon and basic spinal cord structure through TUNEL, luxol fast blue, hematoxylin-eosin staining respectively.ResultsAt the time of8w post injury the BBB score of groupⅣ(10.70±1.22) was significantly higher than the group I (5.53±1.18), group Ⅱ (8.65±1.50), groupⅢ (0.06±1.16)(P<0.05). The observation of HE staining showed that the injured cavity in the group Ⅱ, groupⅢ, groupIVwas significantly smaller than that in the control while group IV was significantly smaller than group Ⅱ amd group Ⅲ Immunohistochemistry staining of GFAP showed the glia scar in the group Ⅱ, group Ⅲ, groupⅣ was significant smaller than the control group while groupⅣ was significantly smaller than group Ⅱ amd groupIII. The amount of positive response cells of NF-200in the group Ⅱ, groupⅢ, group Ⅳ was significant larger than the control group while groupIVwas significantly larger than group Ⅱ amd groupⅢ. Compared with group Ⅱ amd groupⅢ, the vertical section at the epicenter of the injury site stained with luxol fast bule showed more fibers pass through and a remarkable reduction in the area of demyelination in groupIV. The TUNEL positive cells appeared in groupⅣ was significantly lesser than group Ⅱ amd groupⅢ.ConclusionConbined administration of Nafamostat and Methylprednisolone showed better result in promoting the recovery of hindlimb after spinal cord injury, which gives indication for research and clinical practice for the treatment of spinal cord injury.