Effect of Sphingosine 1-Phosphate on the Increased Microvessel Permeability Induced by H₂O₂

OBJECTIVE To study the effect of sphingosine 1-phosphate (S1P) on the increased microvessel permeability of rat induced by hydrogen peroxide(H2O2). METHODS The method of rat mesenteric microvascular perfusion in vivo was used. Microvessel permeability was assessed by measuring hydraulic conductivity(Lp). The microvessel were stained with immunofluorescence technique and examined with laser confocal microscopy to observe the effect of S1P on the changes of vascular endothelial-cadherin (VE-Cadherin) and F-actin caused by H2O2. RESULTS H2O2 increased Lp to 6.1±0.9 times of the control(P<0.01), but after pretreatment with S1P, H2O2 did not give rise to a further significant change. Immunofluorescence study showed that H2O2 could change F-actin cytoskeletal architecture. F-actin arranged disorderly and irregularly. Formation of stress fiber was observed in the middle part of cell. H2O2 could also restructure VE-Cadherin. Detachment of adherent junction and formation of endothelial gap was observed. Pretreatment with S1P could inhibit the change of VE-Cadherin and F-actin induced by H2O2. CONCLUSION S1P can improve the increased microvessel permeability caused by H2O2, which might mediated by inhibiting the formation of stress fibre and endothelial gaps, strengthening adherent junction.