芍药苷改善干燥综合征相关泪腺炎症损伤的作用机制研究OA

AIM:To preliminarily predict the po-tential action direction of paeoniflorin in alleviating lacrimal gland inflammatory injury associated with Sjögren's syndrome(SS)based on target screening and pathway analysis,and to provide preliminary validation through molecular docking and animal experiments.METHODS:Candidate targets of paeoniflorin and SS were screened from public databases and subjected to pathway enrichment analysis to identify inflammation-related signaling directions.Molecular docking was then performed to evaluate the binding characteristics between paeoniflorin and key inflammatory proteins.An SS-related dry eye model was established in male NOD/ShiLtJ mice,which were treated with differ-ent doses of paeoniflorin or hydroxychloroquine for four weeks.Tear secretion was measured to assess lacrimal gland function.Histopathological changes were evaluated by hematoxylin–eosin(HE)staining,and the expression levels of inflammatory media-tors and signaling proteins in lacrimal glands were determined using RT-qPCR and western blot.RE-SULTS:Pathway analysis indicated that inflamma-some-related signaling,particularly the NOD-like re-ceptor pathway,may be involved in the action of paeoniflorin.Molecular docking showed that paeoniflorin exhibited favorable binding affinity to NLRP3 and Caspase-1.Animal experiments indicat-ed that paeoniflorin treatment improved tear secre-tion,alleviated lacrimal gland inflammatory infiltra-tion and tissue injury in SS mice,and was accompa-nied by reduced expression levels of IL-6,IL-18,IL-1β,TNF-α,NLRP3,and Caspase-1.CONCLUSION:This study provides preliminary evidence that paeoniflorin may ameliorate SS-related lacrimal gland inflammatory injury,possibly through modu-lation of inflammatory responses and NLRP3/Cas-pase-1–related processes.