有氧运动对酒精性肝损伤小鼠ALT、AST、IL-10和IL-6等的影响
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摘要
目的:建立小鼠酒精性肝损伤模型,探讨有氧运动对小鼠酒精性肝损伤后肝功能的影响以及血液白细胞介素-10(IL-10)、白细胞介素-6(IL-6)和总抗氧化能力(T-AOC)等的变化。方法:40只8周龄小鼠随机分为N组(对照组)、E组(运动组)、AL组(酒精灌胃组)和E+AL组(运动+酒精灌胃组),分别施加有氧运动、酒精灌胃干预。10周后处死取脾脏、肝脏和血清,分别检测IL-10、T-AOC、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷草转氨酶(ALT)、谷丙转氨酶(AST)和IL-6。结果:(1)血清ALT和AST含量,AL组和E+AL组非常显著高于N组(P<0.01),AL组高于E+AL组(P<0.05);(2)脾脏IL-10含量,AL和E+AL组明显高于N组,E组低于N组,E+AL组高于AL组;AL组和E+AL组血清IL-6含量高于N组(P<0.01),E+AL低于AL组(P<0.05);(3)肝脏T-AOC,AL组、E+AL组低于(P<0.01、P<0.05)、E组高于(P<0.05)N组,AL组低于E+AL组(P<0.05);肝脏SOD,与N组比较,AL组(P<0.05)、E+AL组降低、E组升高,E+AL组高于AL组(P<0.05),MDA含量,与N组相比,E组降低(P<0.05),AL组升高(P<0.01);E+AL组显著性低于AL组(P<0.05)。结论:乙醇在肝脏内代谢过程中会引起机体免疫反应和炎症反应,同时导致肝脏的脂质过氧化损伤;适度的有氧运动干预可提高各实验对象抗氧化能力和抗炎能力,促进机体免疫稳定,减轻肝脏脂质过氧化损伤和炎症损伤,对酒精灌胃所致肝细胞损伤、炎症反应具有一定的缓解作用,提高机体免疫稳定能力,但并不能阻止酒精性肝损伤的发生。
Objective: To analyze the changes of liver function,IL-10,IL-6 and T-AOC in mice,intervene by alcoholic and aerobic exercise,to explore its effects on alcoholic liver injury and its mechanism.Methods: 40 mice were randomly divided into control group(N),exercise group(E),alcohol group(AL),exercise plus alcohol group(E + AL),constructing a model of aerobic exercise and alcoholic liver injury.After 10 weeks,taking the serum,liver and spleen,the AST,ALT,IL-10,IL-6,T-AOC,SOD and MDA index were tested.Results:(1) the content of ALT and AST,compared with N group,AL and E + AL group were significantly increased(P < 0.01);group E + AL was significant lower than that in AL group(P < 0.05);(2) the content of IL-10 in spleen lymphocyte,compared with N group,AL and E + AL group are decreased significantly,but E + AL group are increased vs.AL group.The content of serum IL-6,AL and E + AL group were significantly higher than that in N group(P < 0.01),E group was lower,and E + AL was lower than that of AL group(P < 0.05);(3) the level of T-AOC in hepatic tissue,compared with group N,AL and E + AL group were decreased significantly(P < 0.01,P < 0.05),E + AL group was significantly higher than that of AL(P < 0.05);The level of SOD,AL and E + AL group were significantly lower than in group N;E + AL group was raised than AL group(P < 0.05).The content of MDA,compared with that of N group,E group decreased significantly(P < 0.05),AL group was increased significantly(P < 0.01);E + AL group was significantly lower than those in group AL(P < 0.05).Conclusion: Aerobic exercise can improve the ability of anti-oxidation,immunity and inflammation,reduce liver lipid per oxidation and inflammatory injury of liver caused by alcohol,and has a preventive effect on the damage,but can’t prevent the occurring of alcoholic liver injury.
Objective: To analyze the changes of liver function,IL-10,IL-6 and T-AOC in mice,intervene by alcoholic and aerobic exercise,to explore its effects on alcoholic liver injury and its mechanism.Methods: 40 mice were randomly divided into control group(N),exercise group(E),alcohol group(AL),exercise plus alcohol group(E + AL),constructing a model of aerobic exercise and alcoholic liver injury.After 10 weeks,taking the serum,liver and spleen,the AST,ALT,IL-10,IL-6,T-AOC,SOD and MDA index were tested.Results:(1) the content of ALT and AST,compared with N group,AL and E + AL group were significantly increased(P < 0.01);group E + AL was significant lower than that in AL group(P < 0.05);(2) the content of IL-10 in spleen lymphocyte,compared with N group,AL and E + AL group are decreased significantly,but E + AL group are increased vs.AL group.The content of serum IL-6,AL and E + AL group were significantly higher than that in N group(P < 0.01),E group was lower,and E + AL was lower than that of AL group(P < 0.05);(3) the level of T-AOC in hepatic tissue,compared with group N,AL and E + AL group were decreased significantly(P < 0.01,P < 0.05),E + AL group was significantly higher than that of AL(P < 0.05);The level of SOD,AL and E + AL group were significantly lower than in group N;E + AL group was raised than AL group(P < 0.05).The content of MDA,compared with that of N group,E group decreased significantly(P < 0.05),AL group was increased significantly(P < 0.01);E + AL group was significantly lower than those in group AL(P < 0.05).Conclusion: Aerobic exercise can improve the ability of anti-oxidation,immunity and inflammation,reduce liver lipid per oxidation and inflammatory injury of liver caused by alcohol,and has a preventive effect on the damage,but can’t prevent the occurring of alcoholic liver injury.
引文
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[22]Wu K,Bi Y,Sun K,Wang C.IL-10-producing type 1 regulatory Tcells and allergy[J].Cell Mol Immunol,2007,4:269-275.
[23]Yamaguchi Kanji,Itoh Yoshito,Yokomizo Chihiro,et al.Blockade ofIL-6 signaling exacerbates liver injury and suppresses anti apoptoticgene expression in methionine choline-deficient diet-Fed db/dbmice[J].Laboratory Inverstigation Nvestigation,2011,91(4):609-618.
[24]Lorenz Olga,Parzefall Wolfram,Kainzbauer Eveline,et al.Pro-teomics reveals acute pro-inflammatory and protective responses inrat Kupffer cells and hepatocytes after chemical initiation of livercancer and after LPS and IL-6[J].Proteomics Clinical Applica-tions,2009,3(8):947-967.
[25]Helala,Ghada F.Impact of hepatitis B viral load on serum IL-6,MMP-9 and alpha-fetoprotein levels and their correlation with liverinjury in chronic hepatitis B infection[J].Cytokine,2008,43(3):251-251.
[26]Santos RVT,Viana VAR,Boscolo RA,et al.Moderate exercisetraining modulates cytokine profile and sleep in elderly people[J].Cytokine,2012,60(3):731-735.
[27]陶占泉,陈佩杰,王茹,等.5周递增负荷运动训练过程中T-helper l和T-helper2相关细胞因子基因表达的变化[J].中国运动医学杂志,2006,25(3):271-275.
[28]费云芸.有氧运动对大鼠慢性酒精性肝损伤的影响[J].山东体育学院学报,2010,26(12):47-50.
[29]Mallikarjuna K,Shanmugam K R,Nishanth K,et al.Alcohol-in-duced deterioration in primary antioxidant and glutathione familyenzymes reversed by exercise training in the liver of old rats[J].Alcohol,2010,44(6):523-529.
[30]Yan Bing,Wang Zhao-bao.Effects of ginkgo biloba extract on freeradical metabolism of liver in mice during endurance exercise[J].African Journal of Traditional Complementary and Alternative Medi-cines,2010,7(4):291-295.
[2]Albano E.Alcohol,oxidative stress and free radical damage[J].Proceedings of the Nutrition Society,2006,65(3):278-290.
[3]Zuo G,Gong J,Liu C,et al.Synthesis of toll like receptor 4 inKupffer cells and its role in alcohol-induced liver disease[J].Chi-nese Medical Journal,2003,116(2):297-300.
[4]Song Z,Zhou Z,Deaciuc I,et al.Inhibition of adiponectin produc-tion by homocysteine:a potential mechanism for alcoholic liver dis-ease[J].Hepatology,2008,47(3):867-879.
[5]Wheeler MD.Endotoxin and kupffer cell activation in alcoholic liverdisease[J].Alcohol&Health,2003,27(4):300.
[6]Kuei-Han Tung,Yi-Shin Huang,Kai-Chung Yang,et al.Serum In-terleukin-12 Levels in Alcoholic Liver Disease[J].Journal of theChinese Medical Association,2010,73(2):67-71.
[7]Teresa Auguet,Francesc Vidal,Montserrat Broch,et al.Polymor-phisms in the interleukin-10 gene promoter and the risk of alcohol-ism and alcoholic liver disease in Caucasian Spaniard men[J].Al-cohol,2010,44(3):211-216.
[8]E.González-Reimers,M.J.Sánchez-Pérez,F.Santolaria-Fernández,et al.Changes in cytokine levels during admission and mortality inacute alcoholic hepatitis[J].Alcohol,2012,46(5):433-440.
[9]曹蛟,何应先,肖国强.健步走和太极拳综合练习后非酒精性脂肪肝患者肝损伤及储备功能的变化[J].中国运动医学杂志,2012,31(12):1048-1053.
[10]Shelley E.Keating,Daniel A.Hackett,Jacob George,et al.Exerciseand non-alcoholic fatty liver disease:A systematic review and meta-analysis[J].Journal of Hepatology,2012,57(1):157-166.
[11]Eiichi Yoshimura,Hideaki Kumahara,Takuro Tobina,et al.A 12-week aerobic exercise program without energy restriction improvesintrahepatic fat,liver function and atherosclerosis-related factors[J].Obesity Research&Clinical Practice,2011,5(3):249-257.
[12]Femando P,Bonen A,Hoffman-Goetz L.Predicting sub maximal ox-ygen consumption during treadmill running in mice[J].Can JPhysiol Phamiacol,1993,71:854-857.
[13]赵敏,杨杏芬,黄俊明.小鼠酒精性肝损伤模型的动态研究[J].中国公共卫生,2005,9:1101-1102.
[14]任丽平,杜钢军,崔新萍.蒲公英对酒精性肝损伤的影响[J].中国实验方剂学杂志,2011,17(11):179-181.
[15]徐强,李庆云,吕凤娟,等.牡蛎汤对免疫性肝损伤小鼠血清ALT、AST和肝组织TNF-α的影响[J].中国中医基础医学杂志,2008,14(2):104-105.
[16]Hideki Ohgo,Hirokazu Yokoyama,Hiroshi Hirose,et al.Signifi-cance of ALT/AST ratio for specifying subjects with metabolic syn-drome in its silent stage[J].Diabetes&Metabolic Syndrome:Clini-cal Research&Reviews,2009,3(1):3-6
[17]Goldberg DM,Watts C.Serum enzyme changes as evidence of liverreaction to oral alcohol[J].Gastroenterology,1965,49(3):256-261.
[18]Rohollah Valizadeh,Masoud Nikbakht,Mohsen Davodi,et al.TheEffect of Eight Weeks Elected Aerobic Exercise on the Levels of(AST,ALT)Enzymes of Men Patients with Have Fat Liver[J].So-cial and Behavioral Sciences,2011,15:3362-3365.
[19]龚非力.医学免疫学[M].北京:科学出版社,2007:76-78.
[20]Zeller JC,Panoskaltsis-Mortari A,Murphy WJ,et al.Induction ofCD4+T Cell Alloantigen-Specific Hypo resp on siveness by IL-10and TGF-beta[J].Immunol,1999,163(7):3684-3691.
[21]Polumuri SK,Toshchakov VY,Vogel SN.Role of Phosphatidyl ino-sitol-3 Kinase in Transcriptional Regulation of TLR-Induced IL-12and IL-10 by Receptor Ligation in Murine Macrophages[J].Immu-nol,2007,179(1):236-46.
[22]Wu K,Bi Y,Sun K,Wang C.IL-10-producing type 1 regulatory Tcells and allergy[J].Cell Mol Immunol,2007,4:269-275.
[23]Yamaguchi Kanji,Itoh Yoshito,Yokomizo Chihiro,et al.Blockade ofIL-6 signaling exacerbates liver injury and suppresses anti apoptoticgene expression in methionine choline-deficient diet-Fed db/dbmice[J].Laboratory Inverstigation Nvestigation,2011,91(4):609-618.
[24]Lorenz Olga,Parzefall Wolfram,Kainzbauer Eveline,et al.Pro-teomics reveals acute pro-inflammatory and protective responses inrat Kupffer cells and hepatocytes after chemical initiation of livercancer and after LPS and IL-6[J].Proteomics Clinical Applica-tions,2009,3(8):947-967.
[25]Helala,Ghada F.Impact of hepatitis B viral load on serum IL-6,MMP-9 and alpha-fetoprotein levels and their correlation with liverinjury in chronic hepatitis B infection[J].Cytokine,2008,43(3):251-251.
[26]Santos RVT,Viana VAR,Boscolo RA,et al.Moderate exercisetraining modulates cytokine profile and sleep in elderly people[J].Cytokine,2012,60(3):731-735.
[27]陶占泉,陈佩杰,王茹,等.5周递增负荷运动训练过程中T-helper l和T-helper2相关细胞因子基因表达的变化[J].中国运动医学杂志,2006,25(3):271-275.
[28]费云芸.有氧运动对大鼠慢性酒精性肝损伤的影响[J].山东体育学院学报,2010,26(12):47-50.
[29]Mallikarjuna K,Shanmugam K R,Nishanth K,et al.Alcohol-in-duced deterioration in primary antioxidant and glutathione familyenzymes reversed by exercise training in the liver of old rats[J].Alcohol,2010,44(6):523-529.
[30]Yan Bing,Wang Zhao-bao.Effects of ginkgo biloba extract on freeradical metabolism of liver in mice during endurance exercise[J].African Journal of Traditional Complementary and Alternative Medi-cines,2010,7(4):291-295.