Rongrong Sun1, Qu Zheng2. 1. Department of Nephrology, The First Affiliated Hospital of Hainan Medical College Haikou 570102, Hainan Province, China. 2. Liaoning University of Traditional Chinese Medicine, Center for Post-doctoral Studies Shenyang 110032, Liaoning Province, China.
Abstract
OBJECTIVE: To explore whether protein kinase B (serine/threonrine kinase, AKT)/forkhead box protein O3a (foxo3a) pathway mediates the protective mechanism of resveratrol (RSV) on renal interstitial fibrosis (RIF) and oxidative stress. METHODS: Sprague-Dawley (SD) rats were grouped into Sham group, unilateral ureteral obstruction (UUO) group and UUO + RSV group. HE staining was used to test the pathological damage of RIF intervened by RSV, biochemical analyzer was used to measure serum renal injury indexes (creatinine, Cr, blood urea nitrogen, Bun), and enzyme-linked immunosorbent assay (ELISA) was used to detect oxidative stress indexes (malondialdehyde, MDA; glutathione, GSH; superoxide dismutase, SOD). AKT/FoxO3a signaling pathway markers and renal interstitial indexes were measured by western blot analysis. RESULTS: Compared with Sham group, HE staining in UUO group showed significant RIF pathological damage; Cr and Bun indexes were increased, and AKT/FoxO3a signal pathway was activated, as indicated by increased p-AKT/AKT and p-FoxO3a/FoxO3a; TGF-β1 and α-SMA protein levels in fibrosis indexes were increased, while E-cadherin decreased; MDA was increased, GSH and SOD were decreased in oxidative stress indexes, while those in UUO + RSV group were improved. CONCLUSION: AKT/foxo3a signaling pathway mediates the protective mechanism of RSV on RIF and oxidative stress in UUO rats, and RSV can improve RIF and oxidative stress in UUO rats by inhibiting AKT/foxo3a signaling pathway. AJTR
OBJECTIVE: To explore whether protein kinase B (serine/threonrine kinase, AKT)/forkhead box protein O3a (foxo3a) pathway mediates the protective mechanism of resveratrol (RSV) on renal interstitial fibrosis (RIF) and oxidative stress. METHODS: Sprague-Dawley (SD) rats were grouped into Sham group, unilateral ureteral obstruction (UUO) group and UUO + RSV group. HE staining was used to test the pathological damage of RIF intervened by RSV, biochemical analyzer was used to measure serum renal injury indexes (creatinine, Cr, blood urea nitrogen, Bun), and enzyme-linked immunosorbent assay (ELISA) was used to detect oxidative stress indexes (malondialdehyde, MDA; glutathione, GSH; superoxide dismutase, SOD). AKT/FoxO3a signaling pathway markers and renal interstitial indexes were measured by western blot analysis. RESULTS: Compared with Sham group, HE staining in UUO group showed significant RIF pathological damage; Cr and Bun indexes were increased, and AKT/FoxO3a signal pathway was activated, as indicated by increased p-AKT/AKT and p-FoxO3a/FoxO3a; TGF-β1 and α-SMA protein levels in fibrosis indexes were increased, while E-cadherin decreased; MDA was increased, GSH and SOD were decreased in oxidative stress indexes, while those in UUO + RSV group were improved. CONCLUSION: AKT/foxo3a signaling pathway mediates the protective mechanism of RSV on RIF and oxidative stress in UUO rats, and RSV can improve RIF and oxidative stress in UUO rats by inhibiting AKT/foxo3a signaling pathway. AJTR