依帕司他对2型糖尿病大鼠肝损伤的作用

doi:10.3969/j.issn.1006-7795.2017.02.021

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (2): 268-276.doi: 10.3969/j.issn.1006-7795.2017.02.021

依帕司他对2型糖尿病大鼠肝损伤的作用

赵月蓉^1,2, 侯碧玉², 柳晨歌², 王晓波^1,2, 杜冠华², 张莉², 管淑玉¹

1. 广东药科大学中药学院, 广州 510006;
2. 中国医学科学院药物研究所靶点研究与新药筛选北京市重点实验室, 北京 100050

收稿日期:2016-12-15 出版日期:2017-03-21 发布日期:2017-04-17
通讯作者: 管淑玉,E-mail:guanshy3@163.com;zhangli@imm.ac.cn E-mail:guanshy3@163.com;zhangli@imm.ac.cn
基金资助:
“重大新药创制”科技重大专项（2013ZX09508104）

Effect of epalrestat on liver injury in type 2 diabetic rats

Zhao Yuerong^1,2, Hou Biyu², Liu Chenge², Wang Xiaobo^1,2, Du Guanhua², Zhang Li², Guan Shuyu¹

1. School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China;
2. Beijing Key Laboratory of Drug Target Research and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China

Received:2016-12-15 Online:2017-03-21 Published:2017-04-17
Supported by:
This study was supported by National Science and Technology Major Projects for “Major New Drugs Innovation and Development” (2013ZX09508104)

摘要/Abstract

摘要： 目的探讨依帕司他对2型糖尿病大鼠肝损伤的作用及机制。方法 SD大鼠经高糖高脂饮食喂养联合腹腔注射45 mg·kg^-1链脲佐菌素（Streptozotocin，STZ）建立2型糖尿病大鼠模型，将造模成功的大鼠分为模型对照组，依帕司他组（100 mg·kg^-1）。另取12只正常SD大鼠设为正常对照组。依帕司他组连续8周灌胃给药，模型对照组和正常对照组给予0.5%（质量分数）羧甲基纤维素钠。观察依帕司他对2型糖尿病大鼠体质量、进食饮水量、血糖、血脂、肝功能、肝脏组织学及氧化应激反应的影响，并采用免疫组织化学方法检测肝脏组织中α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）和转化生长因子-β1（transforming growth factor-β1，TGF-β1）表达。结果与模型对照组比较，给药8周后，依帕司他组大鼠空腹血糖和血脂降低，氧化应激反应降低，肝功能明显改善。病理学检查结果表明伊帕司他组大鼠肝脏炎性反应和纤维化病变较模型对照组减轻。免疫组织化学结果可见依帕司他组大鼠肝组织α-SMA和TGF-β1表达显著低于模型对照组。结论依帕司他能够提高机体抗氧化能力，改善2型糖尿病大鼠氧化应激肝损伤，并且能够通过抑制肝星状细胞（hepatic stellate cell，HSC）的激活改善糖尿病大鼠肝纤维化。

关键词: 依帕司他, 2型糖尿病, 氧化应激, 肝纤维化

Abstract: Objective This study investigated the effect of epalrestat on liver injury in rats with type 2 diabetic mellitus (T2DM). Methods SD rats were fed with high-fat and high-sucrose diet for four weeks, then 45 mg·kg^-1 Streptozotocin (STZ) was injected intraperitoneally to make the animal model of type 2 diabetes. Diabetic rats were divided into two groups as the model group and the epalrestat group (100 mg·kg^-1), another 12 normal SD rats were served as the control group. The diabetic rats were treated with or without epalrestat by gavaging for 8 weeks. Body weight, food and water intake, blood glucose level, blood lipids were measured; liver function, liver pathological changes and oxidative stress were examined. Immunohistochemistry of α-smooth muscle actin (α-SMA)and transforming growth factor-β1 (TGF-β1) were conducted. Results Compared with the model group, epalrestat could reduce the concentration of fasting plasma glucose and blood lipids. The index for liver condition and oxidative stress were down regulated. Pathological examination showed that lesions of hepatic inflammation and fibrosis were significantly alleviated. The expressions of α-SMA and TGF-β1 were markedly reduced in liver tissues of type 2 diabetic rats with the treatment of epalrestat. Conclusion Epalrestat could alleviate liver inflammation and hepatic fibrosis of rats with T2DM via anti-oxidative stress and inhibiting the activation of hepatic stellate cell.

Key words: epalrestat, type 2 diabetic mellitus, oxidative stress, hepatic fibrosis

中图分类号:

赵月蓉, 侯碧玉, 柳晨歌, 王晓波, 杜冠华, 张莉, 管淑玉. 依帕司他对2型糖尿病大鼠肝损伤的作用[J]. 首都医科大学学报, 2017, 38(2): 268-276.

Zhao Yuerong, Hou Biyu, Liu Chenge, Wang Xiaobo, Du Guanhua, Zhang Li, Guan Shuyu. Effect of epalrestat on liver injury in type 2 diabetic rats[J]. Journal of Capital Medical University, 2017, 38(2): 268-276.

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依帕司他对2型糖尿病大鼠肝损伤的作用

Effect of epalrestat on liver injury in type 2 diabetic rats

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