Sea cucumber polysaccharide remodels the immune microenvironment and alleviates diabetic nephropathy via the SIRT1-NCF1-Nrf2 axisOA

Background:To investigate the protective effects of sea cucumber polysaccharide(SCP)against diabetic nephropathy(DN)and their mechanisms in modulating oxidative stress and immune microenvironment via the SIRT1-NCF1-Nrf2 pathway.Methods:DN was induced in mice by streptozotocin and treated with different doses of SCP.Renal function,oxidative stress,and pro-inflammatory cytokines were measured.Kidney tissues were examined by H&E staining for glomerular structure and mesangial expansion.qRT-PCR and Western blot assessed the expression of SIRT1,p-NCF1(phosphorylated NCF1 at Ser345),and Nrf2.Results:SCP improved renal function,restored glomerular structure,and reduced mesangial expansion.Pro-inflammatory cytokines IL-6 and TNFαwere reduced.Mechanistically,SCP upregulated SIRT1 and Nrf2,inhibited p-NCF1 protein expression level,alleviating oxidative stress and inflammation.SCP promoted the polarization of macrophages from the M1 phenotype to the M2 phenotype.Also,SCP reduced high glucose-induced oxidative stress and apoptosis in HK-2 cells.Conclusion:SCP exerts protective effects in DN mice by modulating the SIRT1-NCF1-Nrf2 pathway and remodeling the immune microenvironment,thereby providing experimental evidence and potential therapeutic targets for the prevention and treatment of DN.