关键词: 脓毒症, 免疫抑制, Wnt信号通路, 重组人心房钠肽

Abstract: Objective To investigate the effects of recombinant human atrial natriuretic peptide(rhANP) on pulmonary immune suppression in sepsis and its underlying mechanisms.Methods A murine "second-hit" model was established by cecal ligation and puncture(CLP) followed by intratracheal LPS injection.Male C57BL/6 mice were randomized into the Sham operation group (Sham group, 6 mice), the CLP group (44 mice), and the CLP+rhANP (1 mg/kg) group (42 mice).Survival rate,lung wet-to-dry weight ratio,and histopathology were assessed.Proportions of regulatory T cells(Tregs) and myeloid derived suppressor cells(MDSCs) in lung tissue were analyzed by flow cytometry.Expression of inflammatory cytokines(IL-6,IL-17A,IL-10) and Wnt pathway components(Wnt5a,β-catenin,Lef1) was determined by Western blot.Results Compared with the sham group,CLP mice showed significantly increased proportions of Tregs and MDSCs,elevated IL-10 but decreased IL-6 and IL-17A levels,and downregulated Wnt signaling components(all P<0.05).rhANP treatment reversed these immune suppression indicators,improved survival,and activated the Wnt pathway in alveolar macrophages.Conclusion rhANP may alleviate sepsis-induced pulmonary immune suppression by activating the Wnt signaling pathway in alveolar macrophages.

Key words: sepsis, immune suppression, Wnt signaling pathway, recombinant human atrial natriuretic peptide