| Objectives:Spinal cord injury has a very high disability rate,which brings serious public health problems and huge economic burden to the society and family.In particular,iatrogenic spinal cord injury secondary to spinal surgery is a catastrophic event.The occurrence of iatrogenic spinal cord injury is a potentially life-changing event for both the patient and the physician.The changes of spinal cord blood flow play an extremely important role in the pathophysiological process of both primary and secondary spinal cord injury.Studies have shown that spinal column shortening can reduce the neurologic complications of spinal orthopedic surgery,and spinal column shortening can also affect the spinal cord blood flow.In this study,a canine model based on posterior vertebral column resection(PVCR)was established.The spinal column shortening was performed before and after spinal angulation to simulate clinical PVCR operation.The effects of spinal column shortening on spinal cord blood flow,nitric oxide and endothelin were investigated.The underlying molecular mechanism was revealed in a panoramic manner by using differential proteomics.Then,PVCR combined with spinal column shortening was applied in clinical treatment of thoracic and lumbar fracture patients with severe spinal cord injury to investigate the effect of spinal column shortening on spinal cord blood flow and neurological function improvement of the injured spinal cord in clinical patients.Methods:1.The effects of spinal column shortening on spinal cord blood flow during PVCR and spinal column angulation:43 experimental canines were included in this study,of which 3 were blank control group(0 group),and only PVCR surgery was performed without any intervention.The other 40 were divided into A group and B group according to experimental design and purpose.A total of 20 experimental canines in group A underwent different degrees of spinal column shortening and then the spinal column was angulated to 40°.Al group:without spinal column shortening,angulated to 40°;Group A2:1/4 height of the vertebral segment shortening,and then angulated to 40°;A3 group:2/4 height of the vertebral segment shortening,and then tangulated to 40°;A4 group:3/4 height of the vertebral segment shortening,and then angulated to 40°.A total of 20 experimental canines in group B were treated with different interventions after spinal cord injury caused by spinal angulation.Group B1:treated with simple spinal reduction alone after spinal cord injury;Group B2:treated with spinal reduction and methylprednisolone therapy after spinal cord injury;Group B3:treated with spinal reduction and then spinal column shortening up to 2/4 height of the vertebral segment after spinal cord injury;B4 group:treated with spinal reduction,spinal column shortening up to 2/4 height of the vertebral segment and methylprednisolone therapy after spinal cord injury.A laser Doppler blood flow monitor was used to monitor the microcirculation blood flow of the spinal cord at all stages of the experiment.To analyze the effects of different degrees of spinal column shortening on spinal cord blood flow under spinal angulation,and the effects of different intervention programs on spinal cord blood flow in spinal cord angulation injury.2.The effect of spinal column shortening on spinal cord histology and expression of NO and ET-1 during PVCR and spinal column angulation:Spinal cord tissue samples were taken from each group under different intervention,and spinal cord histology was observed by HE staining.The concentration of total nitric oxide(NO)in spinal cord was measured by spectrophotometry.The concentration of endothelin-1(ET-1)in spinal cord was measured by radioimmunoassay.To analyze the effects of different degrees of spinal column shortening on spinal cord tissue,NO and ET-1 under spinal angulation,and the effects of different intervention programs on spinal cord tissue,NO and ET-1 after spinal angulation injury.3.Proteomic study on spinal cord between shortening and non-shortening canines during PVCR and spinal column angulation:Spinal cord tissue of A1 and A3 groups,B1 and B3 groups were taken and the amount of protein between the two groups was detected by TMT proteomics technique.Taken the fold change>1.3 to identify the differentially up-regulated and down-regulated proteins.Bioinformatics analysis was carried out on the function,localization and signaling pathway of the differentially expressed proteins by referring to the bioinformatics database.4.Intraoperative spinal cord blood flow in thoracic and lumbar vertebral fracture patients with severe spinal cord injury treated with PVCR and spinal column shortening:thoracic and lumbar vertebral fracture patients with severe spinal cord injury who received PVCR and spinal column shortening were included in the study,and thoracic and lumbar vertebral fracture patients with severe spinal cord injury who received decompression alone were also included in the study.Basic information,surgical data,imaging data and neurological function of AISA grading before and 1 year after surgery were compared and analyzed between the two groups.At the same time,laser Doppler blood flow monitor was used to monitor the amount of intraoperative spinal cord blood flow in patients with PVCR and spinal column shortening group,and the changes of spinal cord blood flow at different time stages were analyzed.Results:1.After different degrees of shortening and then angulation,the spinal cord blood flow in each subgroup of A group decreased compared with that before intervention,and there were statistically significant differences(p<0.05).Compared with A3 group,the spinal cord blood flow in A4 group and A1 group was statistically different(p<0.05),there was also a statistical difference compared with A2 group(p<0.05).There was no significant difference in spinal cord blood flow between A4 group and A1 group(p>0.05).The A3 group had the least decrease in spinal cord blood flow,only 10.6%.In group B,the spinal cord blood flow of the 4 subgroups after spinal angulation injury was significantly decreased compared with that before injury,with statistically significant differences(p<0.05).Compared with after spinal cord injury,spinal cord blood flow increased significantly after different interventions,with statistical differences(p<0.05).There were differences in the recovery of spinal blood perfusion among all subgroups,and the recovery was the most obvious in B3 and B4 groups,and the difference was statistically significant compared with that in B1 and B2 groups(p<0.05),but there was no statistical difference between B3 group and B4 group(p>0.05).At the same time,there was no statistical difference in spinal cord blood flow after rebound between B1 and B2 groups(p>0.05).2.Histologically,spinal cord injury was the least severe with the 2/4 spine column shortening in both A group and B group.The NO value in 0 group was 29.3±3.3 mmol/L.Using group 0 as the control group,the levels of NO in each of the 4 subgroups in A group were all increased to varying degrees,and there was no statistical difference between group A3 and 0 group(p>0.05),there were statistical differences between the other 3 groups and 0 group(p<0.05).The increase of NO in A4 group was the most significant(45.3±4.2 mmol/L),and the second group was A1 group(41.6±4.1 mmol/L),and the NO value of the two groups was statistically different from that of the A3 group(p<0.05).The ET-1 value of 0 group was 2.410.3ug/g.Compared with the 0 group,ET-1 in the A3 group has a little decreased(2.3±0.2ug/g),and ET-1 in the other three groups increased to different degrees.The increase of ET-1 in A4 group was the most obvious(4.8±0.3ug/g),followed by that in A1 group(3.9±0.2ug/g).Compared with the 0 group,the two groups were significantly increased(p<0.05).Compared with 0 group,NO in each subgroup of group B increased to varying degrees.The increase of NO in B1 group was the most significant(41.4±4.8 mmol/L).The second was NO in group B2(38.7±4.1 mmol/L),and the NO value in two groups was statistically different from that in 0 group(p<0.05).The increase of NO in B3 and B4 groups was 33.4±3.8mmol/L and 32.1±4.2mmol/L,respectively.There was no significant difference in NO between the two groups compared with the 0 group(p>0.05).Compared with 0 group,ET-1 in each subgroup of group B was increased with statistical difference(p<0.05).ET-1 in B1 group increased most obviously(4.5±0.6ug/g);ET-1 increased the least in B4 group(3.2±0.4ug/g).There was no statistical difference in ET-1 between B1 and B2 groups(p>0.05),and between B3 group and B4 group(p>0.05).The ET-1 of the B3 group was statistically different from that of the B1 group(p<0.05);There were statistically significant differences in ET-1 between B4 group and B1 and B2 group(p<0.05).3.Compared with A3 group,99 up-regulated proteins and 48 down-regulated proteins were found in A1 group.The main functions of the up-regulated proteins are:fibrin,glycoprotein,haptoglobin,etc.The main functions of down-regulated proteins include collagen,amino acid transporter,fibrillin,etc.KEGG signaling pathway enrichment analysis revealed that the more significantly activated signaling pathways in the non spinal column shorting included ferroptosis,complement and coagulation cascading,and platelet activation pathways,etc.Compared with B3 group,72 up-regulated proteins were found,and 175 down-regulated proteins were found.The main functions of the upregulated proteins are:proteoglycan connectin,membranin,lipoprotein and histone,etc.The main functions of down-regulated proteins are lactoferrin,anexin,apolipoprotein and myelin basic protein.KEGG signaling pathway enrichment analysis revealed that the more significantly activated signaling pathways in the non spinal column shorting included ferroptosis,tight linkage and complement and coagulation cascading pathways.4.A total of 17 cases were included in the PVCR combined with spinal column shortening group and 16 cases were included in the decompression alone group.There were no statistically significant differences in age,gender,injury mechanism and injury type between the two groups,and no statistically significant differences in preoperative AISA grading between the two groups(p>0.05);Compared with the PVCR&shortening group,the surgical blood loss,operative time and fixed fusion level in the decompression alone group were all less,and the differences were statistically significant(p<0.05).Spinal cord blood flow increased by an average of about 123%from baseline after VCR.Each subsequent spinal column shortening was accompanied by an average increase of about 140%from baseline for the first shortening and 159%from baseline for the last shortening.Spinal cord blood flow increased by an average of about 149%from baseline at the end of the fixation procedure.The difference in the recovery rate between the two groups has clinically significant:the average recovery in the PVCR&shortening group was 1.65 grade,while it in the decompression alone group was 1.25 grade.82%patients of the PVCR&shortening group had at least 1 grade recovery and it was 75%in decompression alone group.The proportion of complete recovery of neurologic function in PVCR&shortening group was 29.4%,and it was 18.8%in the decompression alone group.Conclusions:1.Proper spinal column shortening can protect the spinal cord blood flow during the process of orthopedic spinal angulation.At the same time,in the case of spinal cord injury caused by spinal angulation,the spinal cord blood flow can be improved by appropriate spinal column shortening in addition to routine procedures,so as to reduce spinal cord ischemia injury.2.Proper spinal column shortening can limit the excessive release of NO and ET-1 in the local spinal cord under spinal angulation during orthopedics,thereby reducing the secondary pathophysiological process after spinal cord injury and reducing the degree of spinal cord injury.3.Compared with spinal column shortening,there were significant differential protein expressions in the spinal cord under the condition of spinal angulation in the non-spinal column shortening,and the differential proteins were mainly concentrated in ferroptosis and complement and coagulation cascading pathways.This suggests that proper spinal column shortening is beneficial to avoid ferroptosis in the spinal cord,and thus has a protective effect on the spinal cord.4.PVCR combined with spinal column shortening is beneficial to improve the intraoperative spinal cord blood flow in thoracic and lumbar fracture surgery,and can also obtain a good clinical effect. |
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