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CJAP ›› 2017, Vol. 33 ›› Issue (2): 128-131.doi: 10.12047/j.cjap.5466.2017.033

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The protective effect of exenatide on the renal injury in diabetic rats

HUANG Qiong-zhu3, LIU Xiao-meng1, HUANG Guo-quan1, WANG Li-juan1, ZHENG Yu-jie1, CHEN Xin-cheng1, LIU Li-bin2, CHEN Zhou1   

  1. 1. College of Pharmacy, Fujian Medical University, Fuzhou 350122;
    2. Fujian Institute of Endocrinology, Department of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou 350001;
    3. Department of Endocrinology, the 476 th Hospital of People's Liberation Army, Fuzhou 350002, China
  • Received:2016-06-20 Revised:2016-12-14 Online:2017-03-28 Published:2018-06-20
  • Supported by:
    福建省科技厅重点项目(2013Y0041)福建省财政厅专项资助(2012B022);国家卫计委共建科学基金-福建省卫生教育联合攻关计划(wkj-fj-12)

Abstract: Objective: To investigate the protective effect of exenatide (Ex) on the renal injury in streptozotocin-induced diabetic rats. Methods: Sprague-Dawley rats were randomly divided into 2 groups:normal control group (NC group, n=8) and model group. Model group was injected with low dose of streptozotocin (30 mg·kg-1) after the rats were fed with high fat and high glucose diet for 4 weeks. Seventy-two hours later, rats of blood glucose level ≥ 16.7 mmol·L-1 were divided into diabetes mellitus group (DM, n=10) and two exenatide-treated groups (Ex groups,3 or 6μg·kg-1, n=8). Ex groups subcutaneously injected with exenatide for 12 weeks, but NC group and DM group were injected with the same volume of solvent. Changes in glycolipid metabolism and renal function such as serum creatinine (Scr), urine creatinine (Ucr), blood urea nitrogen (BUN), 24 hour urine micro-albumin (24 h UMA)in the 4 groups of rats were determined and creatinine clearance rate (Ccr) were calculated. Renal oxidative stress parameters such as superoxide dismutase (SOD), malondialdehyde(MDA), glutathione per-oxidase (GSH-Px) were measured. Hematoxylin-eosin (HE) staining was used to examine pathological morphology in the renal tissues and ELISA was performed to determine the level of advanced glycation end products(AGEs), the glycosylation end product in renal tissues. Results: Compared to the DM group,glycolipid metabolic abnormalities in the exenatide-treated groups were significantly ameliorated with lower levels of blood glucose,HbAlc, cholesterol and triglyceride (P < 0.05). The renal function index was markedly improved (P < 0.05) with Ccr reduced, indicating a high glomerular filtration status. Meanwhile, exenatide treatment improved the diabetes-induced pathological changes in renal morphology, substantially increased the activities of SOD and GSH-Px, and reduced the levels of MDA and AGEs. Conclusion: Exe-natide has the renal protective effect probably by the mechanisms of inhibition of AGEs production and reduction of oxidative stress in the renal tissues of diabetic rats.

Key words: exenatide, diabetes nephropathy, advanced glycation end products, oxidative stress

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