摘要
目的:观察黄芪散对高脂饮食诱导的肥胖大鼠肝脏内质网应激信号通路的影响,并探讨其机制。方法:选择雄性SD大鼠,通过高脂饲料连续喂养7周建立肥胖大鼠模型后,将其随机分为模型组,黄芪散低、高剂量组(1. 2,2. 4 g·kg-1),立普妥组(2 mg·kg-1),模型组和正常组给予等量生理盐水,灌胃给药,连续15周。分别测定各组大鼠的体质量、附睾脂肪系数、肝脏系数;采用生化试剂测定血浆空腹血糖(FPG),总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C)的水平;采用苏木素-伊红(HE)染色法观察各组大鼠附睾脂肪及肝脏病理变化;同时采用蛋白免疫印迹法(Western blot)检测肝组织中固醇调节元件结合蛋白-1c(SREBP-1c),蛋白激酶R样内质网激酶(PERK),肌醇依赖酶1α(IRE1α),磷酸化IRE1α(p-IRE1α)的蛋白表达水平。结果:与正常组比较,模型组大鼠的体质量和肝脏系数显著升高(P <0. 01);FPG,TC,TG,LDL-C水平均明显升高(P <0. 05,P <0. 01)。模型组大鼠的脂肪细胞和肝细胞体积明显增大,细胞中可见大量脂肪小泡。同时肝组织中内质网应激相关因子SREBP-1c,PERK,IRE1α,p-IRE1α的蛋白表达明显升高(P <0. 05,P <0. 01)。与模型组比较,黄芪散高、低剂量组均能明显降低肥胖大鼠的体质量、附睾脂肪系数、肝脏系数和糖脂水平(P <0. 05,P <0. 01),且能明显改善附睾脂肪和肝脏的病变程度。黄芪散高、低剂量组及立普妥组大部分可不同程度地降低肝组织中SREBP-1c,PERK,IRE1α/p-IRE1α的蛋白表达水平(P <0. 05,P <0. 01)。结论:黄芪散具有调节糖脂代谢、保护肝脏和减轻体质量的作用,其机制可能与调控肝脏内质网应激相关因子SREBP-1c,PERK,IRE1α/p-IRE1α的蛋白表达有关。
Objective:To explore the effect of Huangqisan on endoplasmic reticulum stress signaling pathway in liver tissues of high-fat diet-induced obese rats and its mechanisms.Method:Male SD rats were selected and fed with high-fat diet for 7 weeks continuously to establish an obese rat model.Then,the rats were randomly divided into model group,low and high-dose Huangqisan group(1.2,2.4 g·kg-1),and Lipitor group(2 mg·kg-1),and orally administered with drugs for 15 consecutive weeks.The control group and the model group were perfused with the same volume of normal saline.The body weight,epididymal fat coefficient and liver coefficient of each group were determined separately.Fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C)were determined by biochemical reagent method.The epididymal visceral adipose tissue and liver pathological changes were observed by hematoxylin and eosin(HE)staining.And the protein expression levels of sterol regulation element-binding transcription factor 1(SREBP-1 c),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK),inositol requiring enzyme 1(IRE1α),p-inositol requiring enzyme 1(p-IRE1α)in liver tissues were detected by Western blot methods.Result:Compared with the control group,the body weight,epididymal fat coefficient and liver coefficient of the model group were significantly increased(P<0.01),and the levels of FPG,TC,TG and LDL-C were also higher than those of the control group(P<0.05,P<0.01).The cell volume of epididymal fat and liver in the model group were enlarged,and numerous fat vesicles were observed in the cells.Meanwhile,the protein expression levels of the endoplasmic reticulum stress-related factors SREBP-1 c,PERK,IRE1α/p-IRE1αwere increased(P<0.05,P<0.01).Compared with the model group,high-dose and low-dose Huangqisan groups could significantly reduce the body weight,epididymal fat coefficient,liver coefficient and levels of glucose and lipid(P<0.05,P<0.01),and pathological examination showed that the
作者
李艳
曹美群
陶文聪
李卫民
罗焕敏
吴正治
LI Yan;CAO Mei-qun;TAO Wen-cong;LI Wei-min;LUO Huan-min;WU Zheng-zhi(Integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Guangzhou 510632,China;Shenzhen Municipal Institute of Geriatrics,Shenzhen 518035,China;The First Affiliated Hospital of Shenzhen University(Shenzhen Second People's Hospital),Shenzhen 518035,China;School of Chinese Materia Medica,Guangzhou University of Chinese Medicine,Guangzhou 510006,China))
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第21期6-11,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81803867,81574038)
广东省科技计划项目(2018A0303130078,2015B020211001)
中国博士后科学基金面上项目(2017M622920)
深圳市医疗卫生三名工程项目(SZSM201612049)
深圳市学科布局项目(JCYJ20180508152437368,JCYJ20170412161254416,JCYJ20170413161352000)
国家高技术研究发展技术(863)项目(2014AA020907)
关键词
肥胖
黄芪散
内质网应激
信号通路
obesity
Huangqisan
endoplasmic reticulum stress
signaling pathway
