Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease and to improve advanced kidney injury are required. Berberine (BBR) has preventive effects on diabetes and its complications. This study is to investigate the effects of BBR on the expression of E-prostanoid receptors (EPs) in rats with high-fat diet and streptozotocin (STZ)-induced DN and underlying molecular mechanisms of BBR on DN rats. DN model was induced in male Sprague-Dawley rats with high-fat diet and low dose of STZ injection. BBR (50, 100, 200 mg/kg/d) were orally administered to rats after STZ injection and conducted for 8 weeks. The levels of interleukin-6 (IL-6) and prostaglandin E2 (PGE2) in renal cortex were measured by enzyme-linked immunosorbent assay. Expression of EPs receptors (EP1-EP4) were determined by western blotting. Remarkable renal damage, hyperglycemia and hyperlipidemia were observed in DN rats. BBR could restore renal functional parameters, suppress alterations in histological and ultrastructural changes in the kidney tissues, improve glucose and lipid metabolism disorders, and increase cAMP levels compared with those of DN model group (Wang et al. in Mol Biol Rep 40:2405-2418, 2013). The level of IL-6 and PGE2 were significantly increased in DN model group compared with normal group, BBR could apparently reduced the level of IL-6 and PGE2. Furthermore, the expression of EP1 and EP3 were both increased and EP4 was lessened in the DN model group compared with normal group, BBR could down-regulate total protein expression of EP1 and EP3 of renal cortex in DN rats and up-regulate the expression of EP4, and there is no significant difference on the expression of EP2 among all groups. These studies demonstrate, for the first time, that BBR exerts renoprotection in high-fat diet and STZ-induced DN rats by modulating the proteins expression of EPs in EP-G protein-cAMP signaling pathway.
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