Abstract: BACKGROUND: Dexamethasone is a glucocorticoid drug commonly used for treating diabetic nephropathy in recent years. It can directly act on glomerular podocytes and increase cell survival by inhibiting inflammatory response and stabilizing cell cycle. However, its specific mechanism of action remains unclear.  
OBJECTIVE: To investigate the mechanism of dexamethasone on high glucose-induced oxidative damage to glomerular podocytes.
METHODS: Glomerular podocytes were divided into six groups: group A, routine culture with no treatment; group B, treatment with glucose; group C, treatment with glucose for 48 hours and valsartan for another 24 hours; groups D-F, treatment with glucose for 48 hours and 1×10-7, 1×10-6, 1×10-5 mol/L dexamethasone for another 24 hours, respectively. Specific touchdown nested PCR was used to detect the methylation level of Nogo receptor 1 (NgR1) in cells. MTT method was used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis. Chemiluminescence method was used to detect oxidative damage-related indicators. Immunofluorescence method was used to detect peroxisome proliferator-activated receptor γ expression.  
RESULTS AND CONCLUSION: (1) Compared with group A, group B had significantly increased methylation level of NgR1, cell apoptosis, and malondialdehyde level (P < 0.05), but significantly decreased cell proliferation, superoxide dismutase and glutathione levels, and peroxisome proliferator-activated receptor γ expression (P < 0.05). (2) Compared with group B, group C had significantly decreased methylation level of NgR1, cell apoptosis, and malondialdehyde level (P < 0.05), but significantly increased cell proliferation, superoxide dismutase and glutathione levels, and peroxisome proliferator-activated receptor γ expression (P < 0.05). (3) Compared with group C, groups E and F had significantly decreased methylation level of NgR1, cell apoptosis, and malondialdehyde level (P < 0.05), but significantly increased cell proliferation, superoxide dismutase and glutathione levels, and peroxisome proliferator-activated receptor γ expression (P < 0.05). Moreover, these changes were more obvious in group F than group E (P < 0.05); however, there was no significant difference between groups D and C (P > 0.05). (4) To conclude, dexamethasone can significantly improve oxidative damage to glomerular podoccytes induced by high glucose and promote the expression of peroxisome proliferator-activated receptor γ, which may be related to inhibition of Ngr1 gene methylation.

Key words: glomerular podocyte, high glucose-induced damage, dexamethasone, Ngr1 gene methylation, oxidative damage, peroxisome proliferator-activated receptor γ