Repair Effect Of Progesterone On Spinal Cord Ischemia-reperfusion Injury And Its Mechanism

Objectives To study the effect of progesterone on spinal cord ischemia-reperfusion injury in rabbits by the intervention of progesterone on the spinal cord ischemiareperfusion injury model in rabbits.Methods The rabbit model of spinal cord ischemia and reperfusion was induced by abdominal aorta occlusion,in which 3 rats in the blank control group only underwent surgery without aortic occlusion.;15,after surgery did not given drug intervention;progesterone Group 15,respectively after 0h,24 h,48h intraperitoneal injection of progesterone 8mg/kg.The injured group and progesterone group were sacrificed 3 rabbits after 12 h,24h,36 h,48h and 72 h respectively.The postoperative 24 h,48h and 72 h were selected at three observation points,and the neurological function was evaluated by Tarlov score.The spinal cord tissue samples were collected and the morphological changes of spinal cord were observed by H&E staining.The expression levels of Caspase-8 and p53 protein in the spinal cord tissue were detected by immunohistochemistry,and the number of positive cells was counted.Fresh tissue samples were collected by Western blotting technique to detect the protein expression of p53 at different time points,and then quantitative analysis was performed.Results 1 H&E staining showed that compared with the control group,injury group12 h had no obvious lesions,24 h spinal cord appeared vacuolar degeneration,neuron 48 h neurons began to shrink;apoptosis,tissue edema and bleeding;72h inflammatory cell infiltration;progesterone group after 24 h to 72 h also appeared in injury group similar changes,but save the neurons quantity,bleeding and edema and infiltration of inflammatory cells and other pathological changes with light.2 After 12 h,the number of neurons in the control group,progesterone group,injury group at 24 h after operation;when the number of three groups of rabbit neurons had no significant difference(P >0.05);48h after the operation,the number of neurons and the blank injury group and progesterone group control group decreased significantly(P < 0.05),and the number of neurons in the injury group was significantly less than that of progesterone group(P <0.05);72h after the operation,the number of neuron injury group and progesterone group compared with blank control group and postoperative 24 h and 48 h further decreased(P <0.05),and the number of neurons in the injury group significantly less than progesterone.(P < 0.05).3 12 h after surgery,injury group and progesterone group rabbit nerve function had different degrees of neurological dysfunction,and the degree of damage is more severe injury group(P < 0.05);operation 48 h motor function after injury group was significantly lower than before the rabbit progesterone group compared with postoperative 24 h is slightly lower,but still the the function was significantly higher than that in the injury group(P < 0.05);the operation of 72 h,reduce the injury group and progesterone group rabbit motor nerve function in varying degrees,but the decrease was not statistically significant,and progesterone group were significantly higher than in the injury group(P < 0.05).4 The expression level of the three group of rabbit spinal cord tissue Caspase-8 were compared,12 h,the control group Caspase-8 was the lowest score,injury group were significantly higher than the control group,progesterone group score between two groups;48h,the expression level of injury group and progesterone group of Caspase-8 was further improved,and the injury group the expression level was significantly higher than that of progesterone group;72h,the expression level of Caspase-8 than the injury group 48 h also increased significantly,progesterone group has increased,but the increase was smaller than the injury group.5 The positive cells of p53 statistics found that 24 h,the control group p53 was the lowest score,the highest injury group,progesterone group score between two groups;48h,the expression level of injury group and progesterone group of p53 was further improved,and the injury group expression level was significantly higher than that of progesterone group;72h when the expression level of p53 than the injury group 48 h also increased significantly,progesterone group has increased,but the increase was smaller than the injury group.Conclusions In this study,through the assessment of the different treatment conditions of spinal cord ischemia reperfusion injury of rabbit spinal cord morphology and inflammation,and the possible mechanism was preliminarily found: 1 spinal cord ischemia reperfusion injury after injection of progesterone can significantly reduce spinal cord inflammation,reduce the apoptosis of spinal cord neurons in the spinal cord,2ischemia reperfusion injury after progesterone intervention can significantly improve the motor nerve function recovery;3 spinal cord ischemia reperfusion received progesterone intervention can significantly reduce the expression of Caspase-8 and p53 protein in spinal cord injury,suggesting that progesterone may be by reducing the expression of Caspase-8 and p53 protein can reduce the apoptosis of neurons after spinal cord ischemia.