Expression and significance of pyroptosis-related proteins GSDMD-N and Caspase-1 in vascular endothelial cells of systemic lupus erythematosus mice

HUANG Xing; XIAO Yu-fei; YAN Wen; LUO Li; JIA Chang-sha; YANG Ying

doi:10.13820/j.cnki.gdyx.20250817

Abstract：Objective To preliminarily investigate the relationship between vascular endothelial pyroptosis and the development of systemic lupus erythematosus(SLE),aiming to provide a theoretical foundation for future clinical treatment strategies.Methods Sixteen SPF-grade female Balb/c mice(7-8 weeks old)were randomly divided into a control group and a model group(n=8 each).The SLE model was induced in the model group by intraperitoneal injec-tion of 0.5 mL Pristane,while the control group received an equal volume of 0.9％sodium chloride.Serum levels of anti-dsDNA and anti-Sm antibodies were measured by ELISA,and urine protein was tested to conrfirm successful modeling.Serum levels of interleukin(IL)-1β and IL-18 were measured.Aortic and renal histopathology were assessed via he-matoxylin and eosin(HE)staining.Immunofluorescence double staining was performed on aortic sections to detect the ex-pression and localization of pyroptosis-related proteins gasdermin D-N(GSDMD-N)and Caspase-1 in vascular en-dothelial cells.Results Compared with the control group,lupus model mice showed significantly increased spleen and kidney weights and indices(t=7.889,U=0,t=2.528,t=5.122,P＜0.05),along with elevated serum levels of anti-dsDNA and anti-Sm antibodies(P＜0.001).HE staining revealed endothelial flattening and inflammatory cell infiltra-tion in the aorta,as well as tubular epithelial cell edema and interstitial inflammation in the kidneys.Serum IL-1 β and IL-18 levels were significantly higher in the model group than in controls[(97.1±4.82)ng/L vs.(86.01±6.88)ng/L,t=3.495,P＜0.01;(130.69±6.05)ng/L vs.(123.07±4.78)ng/L,t=2.616,P＜0.05].Immunofluores-cence showed enhanced red fluorescence for GSDMD-N and Caspase-1 co-localized with CD31-positive endothelial cells in the model group,whereas no significant fluorescence was observed in controls.Conclusion Serum levels of IL-1 β and IL-18 were elevated,and expression of GSDMD-N and Caspase-1 was upregulated in the aortic endothelium of SLE model mice induced by Pristane.These findings suggest that pyroptosis of vascular endothelial cells may be involved in the pathogenesis of SLE,offering a novel perspective for understanding disease mechanisms and identifying potential therapeutic targets.