运动和饮食调整对非酒精性脂肪肝大鼠内质网应激PERK/eIF-2a和IRE-1/XBP-1通路的影响  

The Effect of Exercise and Dietary Modification on PERK/eIF-2a and IRE-1/XBP-1 Pathway Induced by Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease

作　　者：李军汉[1,2] 孙君志[1] 李恩[3] 张仲阳[1] 苏全生[1] 

机构地区：[1]成都体育学院运动医学与健康学院,四川成都610041 [2]北京体育大学研究生院,北京100081 [3]雅安职业技术学院,四川雅安625018

出　　处：《成都体育学院学报》2016年第6期110-113,126,共5页Journal of Chengdu Sport University

基　　金："十二五"国家科技支撑计划重点项目(2012BAK21B01);四川省科技厅应用基础计划项目(2015JY0155);国家体育总局运动医学重点实验室暨运动医学四川省重点实验室资助基金(CTYY2015018)

摘　　要：目的:观察内质网应激PERK/e IF-2a和IRE-1/XBP-1通路在非酒精性脂肪肝(NAFLD)中的变化,探讨运动和饮食调整对非酒精性脂肪肝的干预作用及作用机理。方法:SD雄性大鼠随机分为对照组(20只)和模型组(50只)2组,对照组给予普通饲料喂养,模型组给予高脂饲料喂养。第8周,对照组和模型组各取10只做肝脏病理切片。确定NAFLD模型成功后,模型组随机分为4组:模型组(M)、运动组(EM)、饮食调整组(FM)和运动结合饮食调整组(EFM),每组各10只,对照组剩余10只大鼠编为C组。C组继续普通饲料喂养,M组和EM组继续高脂饲料喂养,FM组和EFM组由高脂饲料改为普通饲料喂养;EM组、EFM组给予有氧游泳运动干预,连续8周,直至第16周实验结束。HE染色观察肝脏病理形态,Western blot检测PERK、e IF-2a和IRE-1、XBP-1蛋白表达,结果:(1)与C组比较,M组肝细胞脂肪变性加重,PERK/e IF-2a和IRE-1/XBP-1通路蛋白表达增加;(2)与M组比较,各干预组肝细胞脂肪变性减轻,PERK/e IF-2a和IRE-1/XBP-1通路蛋白表达降低;(3)M组、EM组、FM组、EFM组4组双因素方差结果示:运动和饮食对PERK/e IF-2a和IRE-1/XBP-1通路蛋白表达具有主效应,且二者具有交互作用。结论:运动和饮食调整对NAFLD发展具有较好的干预作用,且二者联合作用效果更佳,其机制可能与其降低PERK/e IF-2a和IRE-1/XBP-1通路蛋白表达,减少内质网应激有关。Objective ： To observe the change of eIF- 2a PERK/and IRE - 1/XBP - 1 pathway induced by endoplasmic reticulum stress in nonalcoholic fatty liver disease and explore the role of exercise and dietary modification and its mechanism. Methods： 12 rats were randomly selected from 42 rats as the control group, the rest 30 rats were the model group. Control group was fed with ordinary diet, model group was fed with high -fat diet. At the 8th week of experiment, 6 rats in control and model group were respectively chose for liver pathological to determine whether NAFLD model was successfully made. Model group were randomly divided into 4 groups： model group （M）, exercise group （EM）, diet modification group （FM） and exercise combined with diet modification group （ EFM）, each 6 rats. The remaining 6 rats of control group were as C group. Group C was continued to ordinary diet. Group M and EM were continued to high fat diet. Group FM and EFM were fed from high fat diet to ordinary diet. Group EM and EFM were intervened by aerobic swimming exercise for 8 weeks until the end of experiment. We observed the pathological changes in liver tissue by HE staining. Western blot was employed to explore the protein expression of eukaryotic initiation factor 2 α（ eIF-2a） and protein kinase R - like endoplasmic reticulum kinase （PERK） and inositol - requiring Enzyme 1 （ IRE - 1 ） and X - box - binding Protein 1 （ XBP - 1 ）. Results ： （ 1 ） Compared to group C, hepatocyte steatosis is aggravating and pro- tein expression of PERK/eIF -2a and IRE - 1/XBP - 1 pathway gene increased in M group; （2） Compared to group M, liver steatosis relived and protein expression of PERK/eIF - 2a and IRE - 1/XBP - 1 pathway gene reduced in intervention groups ; （ 3 ） The result of two - way anova in Group M and EM and FM and EFM showed that exercise and diet had a main effect on protein expression of PERK/eIF - 2a and IRE - 1/XBP - 1 pathway gene and they had a interactive effect. Conclusions： Exercise a

关 键 词：内质网应激 非酒精性脂肪肝 运动 饮食 

分 类 号：R575.5[医药卫生—消化系统]