基于Nrf2/GPX4信号通路探讨车前子多糖抗肾纤维化的作用及机制OA

Objective To investigate the effect and mechanism of plantaginis polysaccharides against renal fibrosis based on the nuclear factor E2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)signaling pathway.Methods The experiment was conducted from August to December 2025.A total of 30 male Dahl salt-sensitive rats were randomly divided into the five groups:the low-salt group,the low-salt+plantaginis polysaccharides group,the high-salt group,the high-salt+plantaginis polysaccharides group,and the high-salt+plantaginis polysaccharides+ML385 group,6 rats in each group.The rats in the low-salt group and the low-salt+plantaginis polysaccharides group were fed diet containing 0.3%sodium chloride solution;rats in the high-salt group,the high-salt+plantaginis polysaccharides group,and the high-salt+plantaginis polysaccharides+ML385 group were fed diet containing 8.0%sodium chloride solution.Meanwhile,rats in the low-salt+plantaginis polysaccharides group,and the high-salt+plantaginis polysaccharides group were administered plantaginis polysaccharides,and rats in the high-salt+plantaginis polysaccharides+ML385 group were additionally injected intraperitoneally with ML385 based on the high-salt+plantaginis polysaccharides group.All groups were intervened for 4 weeks.After 4 weeks of intervention,renal pathological changes in the five groups of rats were observed,and urinary protein,and serum creatinine,malondialdehyde(MDA),superoxide dismutase(SOD)and Fe2+in renal tissue homogenate,α-smooth muscle actin(α-SMA)and fibronectin(FN)expression levels in renal tissue,mRNA relative expression levels of Nrf2 and GPX4 in renal tissue,protein relative expression levels of Nrf2 and GPX4 in renal tissue were compared among the five groups.Results The urinary protein,serum creatinine,and MDA,Fe2+in renal tissue homogenate in the high-salt group were higher than those in the low-salt group,SOD in renal tissue homogenate was lower than that in the low-salt group(P<0.05).The urinary protein,serum creatinine,and MDA,Fe2+in renal tissue homogenate in the high-salt+plantaginis polysaccharides group were lower than those in the high-salt group,and SOD in renal tissue homogenate was higher than that in the high-salt group(P<0.05).The urinary protein,serum creatinine and MDA,Fe2+in renal tissue homogenate in the high-salt+plantaginis polysaccharides+ML385 group were higher than those in the high-salt+plantaginis polysaccharides group,SOD in renal tissue homogenate was lower than that in the high-salt+plantaginis polysaccharides group(P<0.05).The expression levels of α-SMA and FN in renal tissue in the high-salt group were higher than those in the low-salt group(P<0.05).The expression levels of α-SMA and FN in renal tissue in the high-salt+plantaginis polysaccharides group were lower than those in the high-salt group(P<0.05).The expression levels of α-SMA and FN in renal tissue in the high-salt+plantaginis polysaccharides+ML385 group were higher than those in the high-salt+plantaginis polysaccharides group(P<0.05).The mRNA relative expression levels of Nrf2,GPX4 in renal tissue in the high-salt group were lower than those in the low-salt group(P<0.05).The mRNA relative expression levels of Nrf2,GPX4 in renal tissue in the high-salt+plantaginis polysaccharides group were higher than those in the high-salt group(P<0.05).The mRNA relative expression levels of Nrf2,GPX4 in renal tissue in the high-salt+plantaginis polysaccharides+ML385 group were lower than those in the high-salt+plantaginis polysaccharides group(P<0.05).The protein expression levels of Nrf2,GPX4 in renal tissue in the high-salt group were lower than those in the low-salt group(P<0.05).The protein expression levels of Nrf2,GPX4 in renal tissue in the high-salt+plantaginis polysaccharides group were higher than those in the high-salt group(P<0.05).The protein expression levels of Nrf2,GPX4 in renal tissue in the high-salt+plantaginis polysaccharides+ML385 group were lower than those in the high-salt+plantaginis polysaccharides group(P<0.05).Conclusion Plantaginis polysaccharides can effectively alleviate renal fibrosis and improve kidney function in rats with high salt-induced renal fibrosis,and the mechanism is associated with the inhibition of oxidative stress and ferroptosis by activating Nrf2/GPX4 signaling pathway.