Correlation study on pericyte depletion,eye-signs in blood stasis syndrome,and blood-brain barrier dys-function in neuropsychiatric systemic lupus erythematosus

LI Jianbin; WU Rui

doi:10.3969/j.issn.1006-5725.2025.06.003

Abstract：Objective This study aims to investigate the pathological role and molecular mechanisms of pericyte depletion in neuropsychiatric lupus(NPSLE)and to assess the potential of the PDGFR-β signaling pathway as a novel therapeutic target for NPSLE.Methods NPSLE models were established using 8-week-old female MRL/lpr mice,from which those exhibiting abnormal behaviors were selected for further analysis.The PDGFR-β signaling pathway was modulated using an agonist to promote pericyte proliferation or an inhibitor to suppress pericyte apoptosis.The effects of these treatments on blood-brain barrier(BBB)integrity,eye-signs in blood stasis syndrome,neuronal integrity,and tight junction protein expression were evaluated.Evans blue staining,H&E staining,Nissl staining,and immunofluorescence staining were employed to assess the expression of tight junction proteins(Cadherin,ZO-1),endothelial cell markers(CD31),and pericyte markers(NG2).Results Mice in the NPSLE group exhibited significant anxiety,depression,and cognitive impairment.In the PDGFR-β inhibition group,eye-signs in blood stasis syndrome scores were significantly elevated(P<0.01),BBB permeability was markedly increased(P<0.001),neuronal numbers were significantly reduced,tight junction protein expression was diminished,and pericyte depletion was aggravated.Conversely,the PDGFR-β agonist group showed a significant reduction in eye-signs in blood stasis syndrome scores(P<0.01),improved pericyte survival,enhanced expression of tight junction proteins,reduced neuronal damage,and restoration of BBB function(P<0.001).Immunofluorescence staining further confirmed that PDGFR-β activation significantly protected pericytes.Conclusions Pericyte depletion is closely associated with increased BBB permeability and exacerba-tion of eye-signs in blood stasis syndrome.Modulation of the PDGFR-β signaling pathway may provide a promising therapeutic strategy for NPSLE.