中性粒细胞胞外陷阱网通过促进STAT3磷酸化诱导内皮细胞凋亡参与下肢动脉再狭窄OACSTPCD

Objective To explore the molecular mechanism of neutrophil extracellular traps(NETs)involving in the occurrence and development of arterial restenosis in lower limbs through in vitro and in vivo experiments.Methods The restenosis model was established by guide-wire injury on ApoE-/-C57BL/6 mice,and a sham operation was performed in sham group.The expression of NETs-related proteins and p-STAT3 was detected in two groups.The effects of DNase Ⅰ[10 mL/(kg·d-1)]on neointima formation and STAT3 activation were observed.At the same time,neutrophils were stimulated in vitro and NETs were extracted.The endothelial cells(ECs)were stimulated with the extracted NETs,and the apoptosis of ECs was observed and the expression of p-STAT3 was detected.The level of STAT3 in ECs was knocked down in vitro to observe the effect on the activation of STAT3 downstream and the NETs-induced apoptosis of ECs.Results Compared with sham group,NETs-related proteins and phosphorylation level of STAT3 in restenosis model group were significantly up-regulated.DNase Ⅰ treatment alleviated neointima formation and down-regulate the level of STAT3 phosphorylation.NETs promoted the apoptosis of ECs and up-regulated the phosphorylation level of STAT3 in ECs,while knocking down STAT3 inhibited the phosphorylation of STAT3 and apoptosis of ECs induced by NETs.Conclusion NETs can promote apoptosis of ECs through STAT3 pathway,promote neointima formation and participate in the occurrence and development of restenosis of lower extremity arteryafter vascular injury.