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利拉鲁肽对非酒精性脂肪肝大鼠胰岛素抵抗的改善作用*
引用本文:邢英,李雅丽,郑嵘炅,玛依拉·卡哈尔,木胡牙提·乌拉斯汉. 利拉鲁肽对非酒精性脂肪肝大鼠胰岛素抵抗的改善作用*[J]. 实用肝脏病杂志, 2017, 20(6): 668-671. DOI: 10.3969/j.issn.1672-5069.2017.06.008
作者姓名:邢英  李雅丽  郑嵘炅  玛依拉·卡哈尔  木胡牙提·乌拉斯汉
作者单位:830054 乌鲁木齐市 新疆医科大学第一附属医院内科VIP病区
基金项目:新疆维吾尔自治区科研基金-医学联合基金项目(编号:2015211CO53); 新疆医科大学第一附属医院自然科学基金项目(编号:2014ZRQN24)
摘    要:目的研究利拉鲁肽对非酒精性脂肪性肝病(NAFLD)大鼠胰岛素抵抗(IR)的改善作用。方法取SD大鼠50只,采用高脂饲料喂养法建立NAFLD大鼠模型,将造模成功的32只大鼠随机分为4组,即模型组(A组,n=8),其余3组为不同剂量利拉鲁肽处理组,包括B组【0.9 mg·kg-1·d-1,n=8】、C组【(1.8 mg·kg-1·d-1),n=8】和D组【(3.6 mg·kg-1·d-1,n=8】。在药物干预4 w后,取血和肝脏,制备肝组织匀浆,分别测定大鼠体质量、肝质量、肝指数、血糖、胰岛素(FINS)、血脂(TG、TC)、转氨酶(ALT、AST)、血清丙二醛(MDA)、谷胱甘肽氧化酶(GSH-Px)、肝组织超氧化歧化酶(SOD)、肿瘤坏死因子α(TNF-α)水平。结果与模型组比,药物干预后大鼠体质量、肝指数、血ALT、FINS、FPG、HOMA-IR、MDA和肝组织TG、TC、MDA水平均显著下降(P<0.05),大剂量组上述指标下降显著高于中小剂量组(P<0.05);与模型组比,药物干预后大鼠肝组织GSH-Px和SOD水平均显著升高(P<0.05),且大剂量组升高明显高于中小剂量组(P<0.05);各组间TNF-α变化无明显差异(P>0.05)。结论利拉鲁肽能显著降低NAFLD大鼠血脂和血糖水平,改善IR,治疗作用呈明显的剂量相关性。

关 键 词:非酒精性脂肪性肝病  利拉鲁肽  胰岛素抵抗  谷胱甘肽氧化酶  超氧化歧化酶  大鼠  
收稿时间:2016-12-14

Effects of liraglutide on insulin resistance in rats with nonalcoholic fatty liver disease
Xing Ying,Li Yali,Zheng Rongjiong. Effects of liraglutide on insulin resistance in rats with nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2017, 20(6): 668-671. DOI: 10.3969/j.issn.1672-5069.2017.06.008
Authors:Xing Ying  Li Yali  Zheng Rongjiong
Affiliation:Department of Infectious Diseases,First Affiliated Hospital,Xinjiang Medical University,Urumqi 830054,Xinjiang Uygur Autonomous Region,China
Abstract:Objective To study the effect of different doses of liraglutide on insulin resistance(IR) in model rats with nonalcoholic fatty liver disease(NAFLD). Methods High fat diet was given to 50 male Sprague-Dawley rats to establish NAFLD and 32 rats with successful NAFLD were randomly divided into 4 groups,e.g. group A (model group,n=8),and liraglutide were given in group B [0.9 mg·kg-1·d-1,n=8],group C [1.8 mg·kg-1·d-1,n=8] and group D[3.6 mg·kg-1·d-1,n=8]. Rats were sacrificed after 4 weeks of medicine intervention. Data of body weight and liver weight were recorded. Blood from the abdominal aorta and livers were collected. Liver index,blood glucose,insuli (FINS),blood lipids(TG,TC),transaminase(ALT,AST),malondialdehyde (MDA),and glutathione peroxidase (GSH-Px),superoxide dismutase (SOD) and tumor necrosis factor alpha (TNF-alpha) in liver tissues were detected. Results Compared with in the model group,the rat body weight,liver index,ALT,FINS,FPG,HOMA-IR,MDA in blood and TG,TC,MDA in liver tissues decreased significantly in intervention groups (P<0.05),and in group D with highest dose of liraglutide gained the most decrease in the above index than in the other two intervention groups(P<0.05);Compared with in model group, the GSH-Px and SOD in intervention groups significantly increased(P<0.05),and GSH-Px and SOD in group D increased the most(P<0.05);There was no significant difference of TNF-α among all the groups. Conclusion Liraglutide can significantly reduce the liver index, serum lipid and blood glucose in rats with NAFLD,and improve IR,and the treatment effect is dose-dependent.
Keywords:Nonalcoholic fatty liver disease  Liraglutide  Insulin resistance  Glutathione peroxidase  Superoxide dismutase  Rats  
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