|本期目录/Table of Contents|

耐力训练减轻高脂饮食相关非酒精脂肪肝大鼠肝脏炎症的内质网机制研究

《山东体育学院学报》[ISSN:1006-2076/CN:37-1013/G8]

期数:
2019年05期
页码:
0
栏目:
出版日期:
2019-10-30

文章信息/Info

Title:
-
作者:
江红轲1邵长专1池爱平2
1.上海海事大学文理学院,上海201306;2.陕西师范大学体育学院,陕西 西安710062
Author(s):
-
关键词:
高脂饮食炎症内质网稳态/应激耐力训练
Keywords:
-
分类号:
G804.2
DOI:
-
文献标识码:
A
摘要:
目的:内质网稳态紊乱是炎症发生的关键机制;运动抗炎作用已取得广泛共识,然而运动改善非酒精性脂肪肝(NAFLD)炎症反应的内质网机制尚不清楚。通过高脂饮食(HFD)建立肥胖相关的NALFD模型,以跑台耐力训练为干预手段,监测HFD引起的肝脏炎症事件,并探讨运动抗炎的内质网机制。方法:Sprague-Dawley雄性大鼠80只,随机分成正常饮食组(CON)、正常饮食运动组(CON + AET)、高脂饮食组(HFD)和高脂饮食运动组(HFD + AET)。8周训练结束后采用O油红染色法观察肝脏形态学改变;ELISA法测定肝脏炎症标志物蛋白浓度;Western blot测定内质网稳态标志蛋白及相关炎症调控信号通路。结果:8周高脂饮食后,与对照组相比,模型动物肝细胞脂滴数量显著性增加;炎症趋化因子(IL-6,IL-18,IL-1β和TNF-ɑ)浓度均显著性升高;炎症转录调节因子NF-κB和AP1表达上调,炎症通路ATF6,IRE1α-XBP1/IKK,PERK和IRE1α-eIF2α/JNK被激活;内质网稳态蛋白GRP78和CHOP表达明显增加。相对地,运动干预可明显减少肝脏组织脂滴数量,降低IL-18、IL-1β和TNF-ɑ浓度,失活炎症通路蛋白及炎症转录因子水平,下调GRP78、CHOP蛋白表达。结论:高脂饮食可引起大鼠肝脏内质网稳态紊乱,激活炎症相关信号通路,触发炎症反应;运动干预可有效改善HFD后炎症事件;其中维持内质网稳态及失活相关炎症调节信号级联是其内在关键机制。
Abstract:
-

参考文献/References

[1]Felix D R,Costenaro F,Gottschall C B,et al. Non-alcoholic fatty liver disease (Nafld) in obese children- effect of refined carbohydrates in diet\[J\]. BMC Pediatr,2016,16(1):187. \[2\]Chen L,Chen R,Wang H,et al. Mechanisms Linking Inflammation to Insulin Resistance \[J\]. Int J Endocrinol,2015,(2015):508409. \[3\]Sacerdoti D,Singh S P,Schragenheim J,et al. Development of NASH in Obese Mice is Confounded by Adipose Tissue Increase in Inflammatory NOV and Oxidative Stress\[J\]. Int J Hepatol,2018:3484107. \[4\]Wang L,Chen J,Ning C,et al. Endoplasmic Reticulum Stress Related Molecular Mechanisms in Nonalcoholic Fatty Liver Disease (NAFLD)\[J\]. Curr Drug Targets,2018,19(9):1087-1094. \[5\]Chen Y,Wu Z,Zhao S,et al. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity\[J\]. Sci Rep,2016(6):27486. \[6\]刘倩倩,秦智,侯改霞,等. 有氧运动对NAFLD大鼠肝细胞线粒体结构功能的影响\[J\]. 中国体育科技,2016(5):75-82. \[7\]Guo R,Liong E C,So K F,et al. Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease\[J\]. Hepatobiliary Pancreat Dis Int,2015,14(2):139-144. \[8\]李军汉. 内质网应激介导非酒精性脂肪肝细胞凋亡及运动饮食干预研究\[D\].北京:北京体育大学,2015. \[9\]赵军,史长征,徐晓阳,等. 基于SIRT1轴的线粒体增殖和自噬通路探讨有氧运动对NASH大鼠脂肪性肝炎的影响\[J\]. 北京体育大学学报,2016(1):68-75. \[10\]Zou X,Yan C,Shi Y,et al. Mitochondrial dysfunction in obesity-associated nonalcoholic fatty liver disease:the protective effects of pomegranate with its active component punicalagin\[J\]. Antioxid Redox Signal,2014,21(11):1557-1570. \[11\]Wang Y,Wang S,Wier W G,et al. Exercise improves the dilatation function of mesenteric arteries in postmyocardial infarction rats via a PI3K/Akt/eNOS pathway-mediated mechanism\[J\]. Am J Physiol Heart Circ Physiol,2010,299(6):H2097-H2106. \[12\]Da L G,Frederico M J,Da S S,et al. Endurance exercise training ameliorates insulin resistance and reticulum stress in adipose and hepatic tissue in obese rats\[J\]. Eur J Appl Physiol,2011,111(9):2015-2023. \[13\]Zhang J,Zhang H,Deng X,et al.Baicalin attenuates non-alcoholic steatohepatitis by suppressing key regulators of lipid metabolism,inflammation and fibrosis in mice\[J\].Life Sci,2018,192:46-54. \[14\]柏云,刘志国. 炎症反应在NAFLD发病中的作用研究进展\[J\]. 武汉工业学院学报,2013(4):98-102. \[15\]李军汉,苏全生,孙君志,等. 运动和饮食调整对内质网应激介导非酒精性脂肪肝大鼠模型肝细胞凋亡的影响\[J\]. 中国运动医学杂志,2017(1):36-43. \[16\]Zou X,Yan C,Shi Y,et al. Mitochondrial dysfunction in obesity-associated nonalcoholic fatty liver disease:the protective effects of pomegranate with its active component punicalagin\[J\]. Antioxid Redox Signal,2014,21(11):1557-1570. \[17\]阮凌,李方晖. 运动训练和白藜芦醇保护NAFLD大鼠肝细胞凋亡的内质网应激机制研究\[J\]. 体育科学,2016(8):56-66. \[18\]赵军,赵美琴,史长征,等. 基于SIRT1轴探讨不同强度有氧运动对NAFLD大鼠脂肪性肝炎的影响\[J\]. 体育科学,2014(11):50-59. \[19\]Fakhoury-Sayegh N,Trak-Smayra V,Khazzaka A,et al. Characteristics of nonalcoholic fatty liver disease induced in wistar rats following four different diets \[J\]. Nutr Res Pract,2015,9(4):350-357. \[20\]Chen Z,Yu R,Xiong Y,et al. A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease \[J\]. Lipids Health Dis,2017,16(1):203. \[21\]Ferreira D F,Fiamoncini J,Prist I H,et al. Novel role of TLR4 in NAFLD development:Modulation of metabolic enzymes expression\[J\]. Biochim Biophys Acta,2015,1851(10):1353-1359. \[22\]Zhong Z,Umemura A,Sanchez-Lopez E,et al. NF-kappaB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria\[J\]. Cell,2016,164(5):896-910. \[23\]Panahi G,Pasalar P,Zare M,et al. High glucose induces inflammatory responses in HepG2 cells via the oxidative stress-mediated activation of NF-kappaB,and MAPK pathways in HepG2 cells\[J\]. Arch Physiol Biochem,2018:1-7. \[24\]Thoudam T,Jeon J H,Ha C M,et al. Role of Mitochondria-Associated Endoplasmic Reticulum Membrane in Inflammation-Mediated Metabolic Diseases\[J\]. Mediators Inflamm,2016(2016):1851420. \[25\]Chen A,Liu J,Zhu J,et al. FGF21 attenuates hypoxiainduced dysfunction and apoptosis in HPAECs through alleviating endoplasmic reticulum stress\[J\]. Int J Mol Med,2018,42(3):1684-1694. \[26\]Kim H M,Kim Y,Lee E S,et al. Caffeic acid ameliorates hepatic steatosis and decreased endoplasmic reticulum stress in high-fat diet-induced obese mice by regulating autophagy\[J\]. Nutrition,2018,55-56:63-70. \[27\]阮凌,肖国强,曹姣,等. 运动和白藜芦醇对抑制NAFLD大鼠肝细胞凋亡的作用及机制研究\[J\]. 西安体育学院学报,2014(6):728-734. \[28\]Guo H L,Hassan H M,Ding P P,et al. Pyrazinamide-induced hepatotoxicity is alleviated by 4-PBA via inhibition of the PERK-eIF2alpha-ATF4-CHOP pathway\[J\]. Toxicology,2017,378:65-75. \[29\]Jung T W,Kim H C,Abd E A,et al. Maresin 1 attenuates NAFLD by suppression of endoplasmic reticulum stress via AMPK-SERCA2b pathway\[J\]. J Biol Chem,2018,293(11):3981-3988. \[30\]刘倩倩,肖国强. 游泳运动对肥胖及肥胖抵抗型NAFLD大鼠干预效果的对比研究\[J\]. 体育学刊,2013(1):129-134. \[31\]Da L G,Frederico M J,Da S S,et al. Endurance exercise training ameliorates insulin resistance and reticulum stress in adipose and hepatic tissue in obese rats\[J\]. Eur J Appl Physiol,2011,111(9):2015-2023. \[32\]Passos E,Pereira C D,Goncalves I O,et al. Role of physical exercise on hepatic insulin,glucocorticoid and inflammatory signaling pathways in an animal model of non-alcoholic steatohepatitis\[J\]. Life Sci,2015(123):51-60. \[33\]高珊珊,黄婉婷,闫旋飞,等. 运动对非酒精性脂肪肝脂联素受体后信号传导的影响\[J\]. 沈阳体育学院学报,2015(3):83-88. \[34\]Rada I,Deldicque L,Francaux M,et al. Toll like receptor expression induced by exercise in obesity and metabolic syndrome:A systematic review\[J\]. Exerc Immunol Rev,2018(24):60-71. \[35\]Linden M A,Fletcher J A,Morris E M,et al. Treating NAFLD in OLETF rats with vigorous-intensity interval exercise training\[J\]. Med Sci Sports Exerc,2015,47(3):556-567. \[36\]Kawanishi N,Yano H,Mizokami T,et al. Exercise training attenuates hepatic inflammation,fibrosis and macrophage infiltration during diet induced-obesity in mice\[J\]. Brain Behav Immun,2012,26(6):931-941. \[37\]Hashida R,Kawaguchi T,Bekki M,et al. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease:A systematic review\[J\]. J Hepatol,2017,66(1):142-152. \[38\]Jiang H K,Wang Y H,Sun L,et al. Aerobic interval training attenuates mitochondrial dysfunction in rats post-myocardial infarction:roles of mitochondrial network dynamics\[J\]. Int J Mol Sci,2014,15(4):5304-5322. \[39\]于洋,朱琳,胡敏. 近五年非酒精性脂肪肝运动疗法的研究进展\[J\]. 军事体育学报,2016(4):101-104. \[40\]Wang Y,Tian Z,Zang W,et al. Exercise training reduces insulin resistance in postmyocardial infarction rats\[J\]. Physiol Rep,2015,3(4). \[41\]Nuno-Lambarri N,Barbero-Becerra V J,Uribe M,et al. Mitochondrial Molecular Pathophysiology of Nonalcoholic Fatty Liver Disease:A Proteomics Approach\[J\]. Int J Mol Sci,2016,17(3):281. \[42\]孙易,丁树哲. 内质网-线粒体结构偶联及运动应激研究进展\[J\]. 体育科学,2017(8):50-57. \[43\]Zheng X,Xu F,Liang H,et al. SIRT1/HSF1/HSP pathway is essential for exenatide-alleviated,lipid-induced hepatic endoplasmic reticulum stress\[J\]. Hepatology,2017,66(3):809-824.

备注/Memo

备注/Memo:
国家自然科学基金(No. C050605)。
更新日期/Last Update: 1900-01-01