二氯乙酸盐在脓毒症与肝脏损伤中作用机制的网络药理学与分子对接研究OA

Aim To evaluate the potential of(dichlo-roacetate,DCA)in sepsis and liver injury using net-work pharmacology and molecular docking and to vali-date it through animal models.Methods We predicted DCA's potential drug targets through public data-bases.Further,it used DisGeNET database to collect sepsis and liver damage-related genes,and intersected them with DCA targets to construct a protein-protein in-teraction network between drug targets and disease genes,followed by molecular docking to assess key therapeutic targets.A mouse model of sepsis with liver injury was established.After DCA intervention,liver tissue was collected for mass spectrometry and protein quantification six hours post-intervention,followed by intergroup comparison of DCA-targeted sites.Results Molecular docking indicated that DCA had a strong binding affinity with targets such as PPARA,F2,HSP90AA1,PDK1,ARG1,NOS3 and CAT.In the mouse model,while only CAT and PDK1 exhibited sta-tistically significant differences between the groups.DCA's interactive targets in sepsis and liver injury were mainly enriched in metabolism and immunity-related biological processes.KEGG pathway enrich-ment analysis showed that DCA's interactive disease targets were primarily enriched in the interleukin-17(IL-17)signaling pathway and the Toll-like receptor(TLR)signaling pathway.Conclusion DCA demon-strates significant pharmacological activity in sepsis and liver injury,identifying catalase(CAT)and pyru-vate dehydrogenase kinase 1(PDK1)as potential key targets.