Study on the Effects of Ligustrazine on Gene Expression of Acute Spinal Cord Injury Model Rats Based on Transcriptome Sequencing / 中国药房

ABSTRACT

OBJECTIVE：To investigate the effects of ligustrazine on ge ne expression of acute spinal cord injury （SCI）model rats. METHODS ：Male SD rats were randomly divided into sham operation group （group A ，6 rats），model group （group B ，6 rats at each time point ，12 rats in total ）and ligustrazine intervention group （group C ，6 rats at each time point ，12 rats in total ）. Acute SCI model was established by modified Allen ’s method in group B and C. After modeling ，group C was given ligustrazine 100 mg/kg intraperitoneally ，while group A and B were given constant volume of normal saline intraperitoneally ，once a day ，for consecutive 7 d or 14 d（i.e. group B 7d and B 14d，group C 7d and C 14d）. BBB scoring was conducted in each group before modeling ， 7 and 14 days after modeling. HE and Nissl staining observation were also carried out for spinal cord specimen. The differentially expressed genes （DEGs）between group A and group B ，group B and group C were analyzed by transcriptome sequencing. The enrichment of Gene Ontology （GO）and KEGG signaling pathway was analyzed by GO database and KEGG database. RESULTS ： Compared with group A ，BBB scores of group B were decreased significantly 7 d and 14 d after modeling （P＜0.05），and the number of nerve cells and Nissl body in spinal cord tissue were decreased. Compared with group B ，BBB scores of group C were increased significantly at above time points （P＜0.05），and the number of nerve cells and Nissl body in spinal cord tissue were increased. The numbers of DEGs of group A and group B 7 d， group A and group B 14d，group B 7d and group C 7d，group B 14d FAA380076） and group C 14 d were 886，1 404，70，66，respectively. The genes with opposite expression trend included Ncmap，Prx， Gabrq， Gabrg2， etc. The enrichment cell component ， molecular function ，biological process of DEGs were different 630179114@qq.com in each group ，mainly involving lyocytosis ，lysosome，plasmamembrane，homotype protein binding ，immune response ，ion channel activity ，immune response （group A and B ）；basolateral plasma membrane ，exodeoxyribonuclease activity ，response to INF-γ （group B 7 d and C 7 d）；extracellular domain ，receptor regulatory activity ，phenolic compound metabolism process （group B 14 d and C 14 d）. DEGs enriched in cytokine-cytokine receptor interaction（group A and B ）；CAMs，complement and coagulation cascades and Hedgehog signaling pathway （group B 7d and C 7d）； retrograde endocannabinoid signaling ，neuroactive ligand-receptor interaction ，PPAR signaling pathway ，GABA ergic synapse （group B 14 d and C 14 d），etc. CONCLUSIONS ：Protective effect of ligustrazine on acute SCI model rats may be associated with inflammatory response ，immune response/regulation ，neuron ion channel ，cytokine-cytokine receptor interaction ，neuroactive ligand-receptor interaction and regulation of GABA ergic synapse activity .