宣木瓜多糖缓解PRV感染小鼠脑和肝脏中炎症反应OA

This experiment aimed to elucidate the regulatory effect of Chaenomeles speciosa polysaccharide on the inflammatory response in the brain and liver of mice infected with pseudorabies virus(PRV),and to explore its anti-inflammatory targets by combining differential KEGG pathway mechanisms.Fifty SPF-grade Kunming mice(half male and half female)were randomly allocated into five groups,with 10 mice per group.PRV-infected mice were treated with Chaenomeles speciosa polysaccharide at doses ranging from 50 to 200 mg/kg.A PRV-infected group and a control group were also established.On day 7 of the experiment,the mice were euthanized,and brain and liver tissues were collected.Inflammatory cytokines and the activity of inflammatory effector molecules were detected via ELISA.Meanwhile,transcriptome sequencing was performed on liver tissues,followed by GO and KEGG enrichment analyses,as well as GSEA.The results showed that Chaenomeles speciosa polysaccharide at 50 to 200 mg/kg could ameliorate the imbalance of inflammatory cytokines induced by PRV infection.It reduced the levels of pro-inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-18(IL-18),as well as chemokines including monocyte chemoattractant protein-1(MCP-1),chemokine(C-C motif)ligand 5(CCL5),and C-X-C motif chemokine ligand 10(CXCL10)in both brain and liver tissues.Furthermore,it can inhibit the activity of inflammatory effector molecules cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS).At the transcriptome level,a total of 2 998 differentially expressed genes were identified in the livers of PRV-infected mice after treatment with Chaenomeles speciosa polysaccharide.These differentially expressed genes were significantly enriched in biological processes(such as cellular processes and biological regulation),molecular functions(including binding and catalytic activity),and cellular components(like cellular anatomical entities).KEGG analysis and GSEA yielded consistent results,showing significant enrichment of differentially expressed genes in pathways including the complement and coagulation cascades,hematopoietic cell lineage,extracellular matrix(ECM)-receptor interaction,focal adhesion,phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt)signaling pathway,and mitogen-activated protein kinase(MAPK)signaling pathway.The study indicates that Chaenomeles speciosa polysaccharides can inhibit the excessive inflammatory response in the brain and liver caused by PRV infection by regulating key signaling pathways such as the complement and coagulation cascade,PI3K-Akt and MAPK,and targeting the expression of differentially expressed inflammation-related genes,thereby maintaining the inflammatory homeostasis of the body.