Effect and Mechanism of Total Saponins from Dioscoreae Nipponicae Rhizoma on the Expression of M-type PLA2R and IgG4 in Renal Tissue of Rats with Membra-nous Nephropathy
Objective To investigate the effect of total saponins from Dioscoreae Nipponicae Rhizoma on the ex-pression of M-type phospholipase A2 receptor(PLA2R)and immunoglobulin G4(IgG4)in the renal tissue of rats with membranous nephropathy(MN),as well as to explore the potential underlying mechanisms.Methods Forty male SPF SD rats were divided into five groups by random number table:control,model,benazepril(10 mg/kg),and low-and high-dose saponin groups(total saponins from Dioscoreae Nipponicae Rhizoma,80 mg/kg and 160 mg/kg,respectively),with eight in each group.All groups except the control group were induced with MN using the Border method.After successful modeling,the benazepril group received 10 mg/(kg·d)benazepril by gavage,while the saponin groups received their re-spective doses of total saponins(80 mg/kg and 160 mg/kg)by gavage.The control and model groups were given 10 mL/(kg·d)of normal saline.After four weeks of treatment,24-hour urinary protein,albumin,serum creatinine,blood urea nitrogen,and uric acid were assessed.Renal pathology was observed via HE staining.The expressions of M-type PLA2R,IgG4,phosphorylated phosphoinositide 3-kinase(p-PI3 K),phosphorylated protein kinase B(p-AKT),nuclear factor E2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in renal tissues were detected by Western blot.Results Compared with the model group,the benazepril and high-dose saponin groups showed significant increases in albumin and decreases in serum creatinine,blood urea nitrogen,and uric acid(P<0.05).Renal pathology was notably improved,and the expressions of M-type PLA2R,IgG4,p-PI3K,and p-AKT in the kidneys were reduced,while the expressions of Nrf2 and HO-1 were elevated in both benazepril and saponin groups(P<0.05).Conclusion Total saponins from Di-oscoreae Nipponicae Rhizoma exert protective effects on the kidneys of MN rats.The potential mechanisms may involve down-regulating PLA2R and IgG4,inhibiting the PI3K/AKT pathway,and activating the Nrf2/HO-1 pathway.
Membranous nephropathyTotal saponins from Dioscoreae Nipponicae RhizomaPhospholipase A2 re-ceptorImmunoglobulin G4Phosphoinositide 3-kinase/protein kinase B pathwayNuclear factor E2-related factor 2/heme oxygenase-1 pathway