Panax notoginseng saponins protect kidney from diabetes by up-regulating silent information regulator 1 and activating antioxidant proteins in rats

To explore the mechanism of the protective effects of Panax notoginseng saponins (PNS) on kidney in diabetic rats. Diabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/(kg day) and PNS-200 mg/(kg day) groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7 (BMP-7). Silent information regulator 1 (SIRT1) was silenced in rat mesangial cells by RNA interference. The mRNA expressions of SIRT-1, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta 1 (TGF-beta 1) and plasminogen activator inhibitor-1 (PAI-1) were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor kappa B (NF-kappa B) P65 were determined by western blotting. The concentration of MCP-1, TGF-beta 1 and malondialdehyde (MDA) in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase (SOD) was detected by the classical method of nitrogen and blue four. In diabetic model rats, PNS could not only reduce blood glucose and lipid (P < 0.01), but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1 (P < 0.01) and in turn suppress the transcription of TGF-beta 1 (P < 0.05) and MCP-1 (P < 0.05). PNS could also reverse the increased acetylation of NF-kappa B p65 by high glucose. In addition, redox regulation factor MDA was down-regulated (P < 0.05) and SOD was up-regulated (P < 0.01), which were both induced by SIRT1 up-regulation. PNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-beta 1, as well as activating antioxidant proteins.