Abstract:Objective: To investigate the effect of plantain seed polysaccharide (PSP) on renal tissue injury in diabetic nephropathy (DN) rats by regulating Sirt1-Foxo1 signaling pathway. Methods: A DN rat model was constructed, and successfully modeled rats were assigned into DN group, L-PSP, H-PSP groups (gavage of 400 and 800mg/kg PSP), and H-PSP+EX-527 group (gavage of 800mg/kg PSP+gavage of 5 mg/kg Sirt1 inhibitor EX-527), with 10 rats in each group. Another 10 normal rats were regarded as Control group. The Control group and DN group were given equal amounts of physiological saline once a day for 28 consecutive days. Use a urine protein assay kit to detect 24-hour urinary protein levels; and employ ELISA to measure serum creatinine (SCr) andβ2-microglobulin (β2-MG) levels in rats. HE staining was performed to observe pathological changes in rat kidney tissue. The chemical colorimetric method was performed to detect SOD, MDA, and GSH-Px in rat kidney tissue. ELISA was performed to detect IL-6, TNF-α, and IL-8 in rat serum. Western blot was performed to detect changes in the expression of Sirt1-Foxo1 signaling pathway proteins in rat kidney tissue. Results: Compared with the Control group, the renal tissue of rats in DN group lost normal structure, showed great interstitial inflammatory cells infiltration, enlarged glomeruli, obvious tubular vacuolization with degenerat and ionnecrosis, and increased mesangial matrix; the SCr, β2-MG, 24-hour urinary protein, MDA, IL-6, TNF-α, and IL-8 elevated; and the SOD, GSH-Px, and the Sirt1 and Foxo1 protein expression decreased (P<0.05). Compared with the DN group, the degree of interstitial inflammation cells infiltration in the renal tissue of rats in L-PSP and H-PSP groups decreased, the glomerular structure was basically normal, and the number of vacuoles decreased; the SCr, β2-MG, 24-hour urinary protein, MDA, IL-6, TNF-α, and IL-8 decreased; and the SOD, GSH-Px, and the Sirt1 and Foxo1 protein expression increased (P<0.05). Compared with the H-PSP group, the H-PSP+EX-527 group showed aggravated inflammatory infiltration and increased vacuoles in the renal tissue of rats; the SCr, β2-MG, 24-hour urinary protein, MDA, IL-6, TNF-α, and IL-8 elevated; and the SOD, GSH-Px, and the Sirt1 and Foxo1 protein expression decreased (P<0.05). Conclusion: PSP can alleviate renal injury in DN rats, and its mechanism may be achieved by activating Sirt1-Foxo1 signaling pathway, enhancing the body's antioxidant capacity, and reducing inflammatory factors such as IL-6, TNF-α, and IL-8.