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45mg·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。
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.
作者
赵月蓉
侯碧玉
柳晨歌
王晓波
杜冠华
张莉
管淑玉
Zhao Yuerong Hou Biyu Liu Chenge Wang Xiaobo Du Guanhua Zhang Li Guan Shuyu(School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China Beijing Key Laboratory of Drug Target Research and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China)
出处
《首都医科大学学报》
CAS
北大核心
2017年第2期268-276,共9页
Journal of Capital Medical University
基金
"重大新药创制"科技重大专项(2013ZX09508104)~~
关键词
依帕司他
2型糖尿病
氧化应激
肝纤维化
epalrestat
type 2 diabetic mellitus
oxidative stress
hepatic fibrosis
