Protective effect of resveratrol on kidney in rats with diabetic nephropathy and its effect on endoplasmic reticulum stress

D. Yuan, X.-M. Liu, Z. Fang, L.-L. Du, J. Chang, S.-H. Lin

Department of Nephrology, Yantaishan Hospital, Yantai, Shandong Province, China. Shuhualin0927@163.com

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• Pharmacology

OBJECTIVE: Diabetic nephropathy (DN) can cause chronic renal insufficiency and significantly reduce the life quality of patients with diabetes mellitus, and may eventually lead to death. The study investigated the expression of endoplasmic reticulum stress-related factors, which have important roles in the progress of DN and to explore effects of resveratrol on DN and the possible mechanism.
MATERIALS AND METHODS: Specific pathogen free (SPF) grade healthy male Sprague Dawley (SD) rats were divided into different groups for different treatments. The diabetic rat model was established by intraperitoneal injection of low-dose streptozotocin (STZ) (40 mg/kg). The normal rats and diabetes model rats were divided into four groups including normal control group (N), normal control + resveratrol (N+R), model group (M), and model + resveratrol group (M+R) for different treatments. The changes of renal histology were observed by immunohistochemistry. Glucose oxidase/peroxidase method was used to measure FPG, UP 24 h content was measured by bicinchoninic acid (BCA) assay, BUN, Scr and Cys C content were measured by automatic biochemical analyzer. The expressions of 78 kDa glucose-regulated protein (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP) were analyzed by Western blot.
RESULTS: Resveratrol treatment significantly reduced the fasting blood glucose level, urinary protein level and renal pathological damage. The phosphorylation of PERK in the kidney of rats with diabetes was up-regulated, while resveratrol treatment reduced this change. The expression of p- PERK, GRP78, ATF4, and CHOP was significantly increased in rats with diabetes, while resveratrol treatment can reduce the increased level of those endoplasmic reticulum stress related factors.
CONCLUSIONS: Resveratrol has a good therapeutic effect on DN in rats without side effect. The mechanism may be related to the regulation of endoplasmic reticulum stress response.

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