富含单不饱和脂肪酸饮食对非酒精性脂肪性肝炎大鼠胰岛素敏感性的影响  

Effect of monounsaturated fatty acids-rich diet on insulin sensitivity in rats with non-alcoholic steatohepatitis

作　　者：李楠[1] 徐正婕[2] 段晓燕[2] 郑培奋[1] LI Nan XU Zhengjie DUAN Xiaoyan et al(Department of Gastroenterology, Zhejiang Hospital, Hangzhou 310013, China)

机构地区：[1]浙江医院消化内科,杭州310013 [2]上海交通大学医学院附属新华医院消化科

出　　处：《浙江医学》2017年第11期865-870,共6页Zhejiang Medical Journal

基　　金：王宝恩抗肝纤维化基金项目(20110006)

摘　　要：目的通过观察富含单不饱和脂肪酸(MUFA)和富含饱和脂肪酸(SFA)髙脂饮食(HFD)诱导的非酒精性脂肪性肝炎(NASH)大鼠血清和TNF-α、IL-6、瘦素(LP)和脂联素(APN)水平的变化,探讨MUFA对NASH大鼠胰岛素敏感性的影响及可能的分子机制。方法随机将30只雄性SD大鼠分为3组,分别予正常饲料(C组)、富含MUFA的橄榄油(M组)和富含SFA的猪油(S组)成分的高脂饲料喂养12周,测定体重、肝脏脂质含量、血清转氨酶、血脂、空腹血糖(FBG)和胰岛素(INS)水平,计算胰岛素抵抗指数(HOMA-IR),光镜下观察肝组织病理并计算NAFLD活动度积分(NAS),应用Western-blot半定量胰岛素受体底物-1(IRS-1)蛋白表达,ELISA法检测血清和肝脏TNF-α、IL-6、LP及APN水平。结果高脂饮食12周成功建立大鼠NASH模型。与S组相比,M组体重增长较少(P<0.05),肝脏TG含量减少(P<0.05),HOMA-IR和NAS均下降(P<0.05),肝脏IRS-1蛋白表达上调约60%(P<0.05)。与C组比较,S组血清LP、TNF-α水平升高,且高于M组(P<0.05),血清和肝脏APN水平均下降(P<0.05),但肝脏APN水平与M组差异无统计学意义(P>0.05)。结论长期过量摄入等热量MUFA和SFA均可诱发胰岛素抵抗(IR),导致NASH发生。MUFA对血糖、血脂、肝脂肪含量及IR程度的影响均明显轻于SFA,其机制可能是通过调节脂肪因子分泌,减轻肝脏IR与炎症浸润。Objective To investigate the effects of monounsaturated fatty acids（MUFA） on insulin resistance（IR） in rats with non-alcoholic steatohepatitis（NASH） and its molecular mechanisms.Methods Thirty male Sprague-Dawley rats were randomly divided into 3 groups,fed with normal diet（group C）,high-fat diet with 10% olive oil（group M） or 10% lard（group S） diet for 12 weeks,respectively.The body weight was observed;surum transaminase blood lipids,fasting blood glucose and insulin were measured;live TG and FFA content was determined;and insulin resistance index（HOMA-IR） was calculated.The liver histopathological changes were observed with electron microscope,and the NAFLD activity score（NAS） was obtained.The expression of IRS-1 was detected by Western blot.The levels of TNF-α,IL-6,leptin（LP） and adiponectin（APN） in serum and liver were detected by sandwich enzyme-linked immunosorbant assay（ELISA）.Results The NASH rat model was successfully established with high-fat diets for 12 weeks.Compared with those in group S,the body weight and liver TG content were decreased in group M.HOMA-IR index and NAS in group Mwere lower than those in group S（P〈0.05）.The protein expression of hepatic IRS-1 in group M was increased by 60%,compared to those of group S（P〈0.05）.The serum levels of TNF-α and LP increased in group S,Which were higher than those of group M（P〈0.05）.The serum and liver APN levels in groups M and S decreased significantly,compared with those in group C（P〈0.05）,the liver APN levels between groups M and S was no significant difference（P〈0.05）.Conclusion The long-term excessive intake of MUFA and SFA can induce peripheral and hepatic insulin resistance,resulting in NASH.Effects ofMUFA on plasma glucose and lipid levels,the fat content of liver and IR are significantly lower than those of SFA.MUFA may improve hepatic IR and inflammatory infiltration by regulating the secretion of adipokines.

关 键 词：非酒精性脂肪性肝炎 单不饱和脂肪酸 脂肪因子 胰岛素抵抗 

分 类 号：R575.1[医药卫生—消化系统]