艾塞那肽对糖尿病大鼠肾脏损伤的保护作用

doi:10.12047/j.cjap.5466.2017.033

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (2): 128-131.doi: 10.12047/j.cjap.5466.2017.033

艾塞那肽对糖尿病大鼠肾脏损伤的保护作用

黄琼珠³, 刘潇萌¹, 黄国全¹, 王丽娟¹, 郑玉洁¹, 陈鑫城¹, 刘礼斌², 陈洲¹

1. 福建医科大学药学院, 福州 350122;
2. 福建医科大学附属协和医院内分泌科福建内分泌研究所, 福州 350001;
3. 中国人民解放军第四七六医院内分泌科, 福州 350002

收稿日期:2016-06-20 修回日期:2016-12-14 出版日期:2017-03-28 发布日期:2018-06-20
通讯作者: 陈洲,Tel:13960833981,E-mail:kellandchen1007@Hotmail.com E-mail:kellandchen1007@Hotmail.com
基金资助:
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）

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. 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）

摘要/Abstract

摘要： 目的：探讨GLP-1类似物艾塞那肽（exenatide）对链脲佐菌素诱导的糖尿病大鼠肾脏的保护作用。方法：SD大鼠随机分为正常组（NC组，n=8）和模型组；模型组给予高脂高糖饲料，喂养4周后腹腔注射STZ（30 mg·kg^-1）建模，72 h后以血糖≥ 16.7 mmol·L^-1为糖尿病成模标准，将成模大鼠随机分为糖尿病对照组（DM组，n=10）、3 μg·kg^-1艾塞那肽干预（Ex-1）组和6μg·kg^-1艾塞那肽干预（Ex-2）组；艾塞那肽组连续皮下注射艾塞那肽（bid）12周，NC组和DM组注射等容积溶剂；测定各组大鼠糖脂代谢变化和肾功能指标如血肌酐（Scr）、尿肌酐（Ucr）、尿素氮（BUN）、24 h尿微量白蛋白排出率（24 h UMA）并计算肌酐清除率（Ccr）；测定肾组织氧化应激指标超氧化物歧化酶（SOD）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）；HE染色观察肾组织病理形态及ELISA法测定肾组织糖基化终末产物AGEs水平。结果：与糖尿病组相比，艾塞那肽可明显改善糖尿病大鼠糖脂代谢，血糖、糖基化血红蛋白（HbAlc）、甘油三脂及胆固醇值均下降（P < 0.05），肾功能指标明显好转（P < 0.05）且肌酐清除率下降（P < 0.05），提示肾小球高滤过状态；同时改善糖尿病引起的肾组织病理结构改变，AGEs浓度下降（P < 0.05），氧化应激指标SOD和GSH-Px活力升高，MDA含量降低（P < 0.05）。结论：艾塞那肽具有肾脏保护作用，其机制可能与抑制糖尿病大鼠肾组织的AGEs生成和改善氧化应激有关。

关键词: 艾塞那肽, 糖尿病肾病, 糖基化终末产物, 氧化应激

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

黄琼珠, 刘潇萌, 黄国全, 王丽娟, 郑玉洁, 陈鑫城, 刘礼斌, 陈洲. 艾塞那肽对糖尿病大鼠肾脏损伤的保护作用[J]. 中国应用生理学杂志, 2017, 33(2): 128-131.

HUANG Qiong-zhu, LIU Xiao-meng, HUANG Guo-quan, WANG Li-juan, ZHENG Yu-jie, CHEN Xin-cheng, LIU Li-bin, CHEN Zhou. The protective effect of exenatide on the renal injury in diabetic rats[J]. CJAP, 2017, 33(2): 128-131.

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艾塞那肽对糖尿病大鼠肾脏损伤的保护作用

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

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