跑步运动对小鼠端粒长度和体内氧化抗氧化的影响
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摘要
目的:观察跑步运动对小鼠端粒长度和体内氧化抗氧化的影响,探讨中医学"流水不腐,户枢不蠢"运动养生观的现代生物学机制。方法:选取并将8周龄雄性ICR小鼠随机分为3组(未施加运动组,运动1组,运动2组),两运动组按2种不同的运动量,每天跑步,共运动8周后取材。荧光定量PCR的方法检测血液细胞和肝脏组织中基因端粒的长短变化,化学法测定试剂盒检测肝脏组织中还原型胱甘肽(GSH)/氧化型谷胱甘肽(GSSG)比值的变化,总超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、心肌组织中蛋白质羰基和丙二醛(MDA)的水平,用酶联免疫吸附试验(ELISA)试剂盒检测心肌组织中8-异前列腺素F2α(Direct 8-iso-PGF2α8)的水平和8-羟基脱氧鸟苷(8-OHdG)的水平。结果:运动1组和运动2组血液细胞中端粒的长度均长于未施加运动组,差异有统计学意义(P <0. 05);肝脏组织中端粒的长度,虽长于未施加运动组,但差异无统计学意义(P> 0. 05)。运动1组与未施加运动组比较,小鼠肝组织中GSH/GSSG的比值变大,差异有统计学意义(P <0. 05),运动2组与未施加运动组比较,差异无统计学意义(P> 0. 05);运动1组和运动2组与未施加运动组比较,肝组织中过氧化氢酶(CAT)的水平升高,差异有统计学意义(P <0. 05),3组小鼠肝组织中总超氧化物歧化酶(SOD)水平差异无统计学意义(P> 0. 05)。运动1组和运动2组与未施加运动组比较,8-OHdG水平、蛋白质羰基水平、异前列腺素F2α水平均降低,差异有统计学意义(P <0. 05)。运动1组与未施加运动组比较,丙二醛水平降低,差异有统计学意义(P <0. 05),运动2组与未施加运动组比较,差异无统计学意义(P> 0. 05)。结论:一定强度的运动可以升高抗氧化防御作用,降低氧化损伤,减缓端粒的缩短速度。
Objective: To observe the effects of running exercise on telomere length and the oxidation and antioxidation level in mice,and to explore the modern biological mechanism of exercise in the traditional Chinese medicine. Methods: Eight-week-old male ICR mice were randomly divided into three groups( no exercise group,exercise group 1,and exercise group 2). The two exercise groups were given different amount of daily running for 8 weeks. The quantitative real-time PCR method was used to detect the change of telomere length in blood cells and liver tissue. The chemical assay kit was used to detect the change of glutathione( GSH)/oxidized glutathione( GSSG) in liver tissue,and to detect the change in total superoxide dismutase( SOD),catalase( CAT),protein carbonyl and malondialdehyde( MDA) content in myocardial tissue. The content of 8-isoprostaglandin F2α and 8-hydroxydeoxyguanosine( 8-OHdG) in cardiac muscle tissue were detected using the ELISA kits. Results: Compared with the nonexercise group,the length of telomere in the blood cells of exercise group 1 and exercise group 2 was significantly longer than that of the no exercise group( P < 0. 05 or P < 0. 01). Although longer than the no exercise group,the length of telomeres in liver was not statistical significant. The ratio of GSH/GSSG in liver tissue of mice in exercise group 1 was higher than that in no exercise group,and there was no significant difference between exercise group 2 and non-exercise exercise group. Compared with the non-exercise group,the contents of catalase( CAT) in the liver tissue were significantly higher in exercise group 1 and exercise group 2,the difference was statistically significant( P < 0. 05 or P < 0. 01). No significant difference was found in the total superoxide dismutase( SOD) content in the tissues. Compared with no exercise group,the levels of 8-OHdG,protein carbonyl,and isoprostaglandin F2α in exercise group 1 and exercise 2 group were significantly decreased( P < 0. 05 or P < 0. 01). Compared with the no exercise group,the content of malondialdehyde in the exercise group 1 was decreased,and the difference was statistically significant( P < 0. 05),while there was no significant difference between the exercise group 2 and the no exercise exercise group. Conclusion: A certain intensity of exercise can increase the antioxidant defenses,reduce oxidative damage,and slow down the telomere's shortening.
Objective: To observe the effects of running exercise on telomere length and the oxidation and antioxidation level in mice,and to explore the modern biological mechanism of exercise in the traditional Chinese medicine. Methods: Eight-week-old male ICR mice were randomly divided into three groups( no exercise group,exercise group 1,and exercise group 2). The two exercise groups were given different amount of daily running for 8 weeks. The quantitative real-time PCR method was used to detect the change of telomere length in blood cells and liver tissue. The chemical assay kit was used to detect the change of glutathione( GSH)/oxidized glutathione( GSSG) in liver tissue,and to detect the change in total superoxide dismutase( SOD),catalase( CAT),protein carbonyl and malondialdehyde( MDA) content in myocardial tissue. The content of 8-isoprostaglandin F2α and 8-hydroxydeoxyguanosine( 8-OHdG) in cardiac muscle tissue were detected using the ELISA kits. Results: Compared with the nonexercise group,the length of telomere in the blood cells of exercise group 1 and exercise group 2 was significantly longer than that of the no exercise group( P < 0. 05 or P < 0. 01). Although longer than the no exercise group,the length of telomeres in liver was not statistical significant. The ratio of GSH/GSSG in liver tissue of mice in exercise group 1 was higher than that in no exercise group,and there was no significant difference between exercise group 2 and non-exercise exercise group. Compared with the non-exercise group,the contents of catalase( CAT) in the liver tissue were significantly higher in exercise group 1 and exercise group 2,the difference was statistically significant( P < 0. 05 or P < 0. 01). No significant difference was found in the total superoxide dismutase( SOD) content in the tissues. Compared with no exercise group,the levels of 8-OHdG,protein carbonyl,and isoprostaglandin F2α in exercise group 1 and exercise 2 group were significantly decreased( P < 0. 05 or P < 0. 01). Compared with the no exercise group,the content of malondialdehyde in the exercise group 1 was decreased,and the difference was statistically significant( P < 0. 05),while there was no significant difference between the exercise group 2 and the no exercise exercise group. Conclusion: A certain intensity of exercise can increase the antioxidant defenses,reduce oxidative damage,and slow down the telomere's shortening.
引文
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[20]Maes M,Galecki P,Chang YS,et al.A review on the oxidative and nitrosative stress(O&NS)pathways in major depression and their possible contribution to the(neuro)degenerative processes in that illness[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(3):676-692.
[21]Borgstahl GEO,Oberley-Deegan RE.Superoxide Dismutases(SODs)and SOD Mimetics[J].Antioxidants(Basel),2018,7(11):156-159.
[22]Glorieux C,Calderon PB.Catalase,a remarkable enzyme:targeting the oldest antioxidant enzyme to find a new cancer treatment approach[J].Biol Chem,2017,398(10):1095-1108.
[23]Schmitt B1,Vicenzi M2,Garrel C3,et al.Effects of N-acetylcysteine,oral glutathione(GSH)and a novel sublingual form of GSH on oxidative stress markers:A comparative crossover study[J].Redox Biol,2015,6:198-205.
[24]Dabrowska N,Wiczkowski A.Analytics of oxidative stress markers in the early diagnosis of oxygen DNA damage[J].Adv Clin Exp Med,2017,26(1):155-166.
[25]Tian F,Tong TJ,Zhang ZY,et al.Age-dependent down-regulation of mitochondrial 8-oxoguanine DNA glycosylase in SAM-P/8 mouse brain and its effect on brain aging[J].Rejuvenation Res,2009,12(3):209-215.
[26]Zheng J,Bizzozero OA.Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion[J].Free Radic Res,2010,44(3):258-266.
[27]Ayala A,Mu1oz MF,Argüelles S.Lipid peroxidation:production,metabolism,and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal[J].Oxid Med Cell Longev,2014,2014:360438.
[28]Roberts LJ,Morrow JD.Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo[J].Free Radic Biol Med,2000,28(4):505-513.
[2]陈奇猷.吕氏春秋校释[M].上海:学林出版社,1984:136.
[3]Arsenis NC,You T,Ogawa EF,et al.Physical activity and telomere length:Impact of aging and potential mechanisms of action[J].Oncotarget,2017,8(27):45008-45019.
[4]Müezzinler A,Zaineddin AK,Brenner H.A systematic review of leukocyte telomere length and age in adults[J].Ageing Res Rev,2013,12(2):509-519.
[5]Maxwell F,Mc Glynn LM,Muir HC,et al.Telomere attrition and decreased fetuin-A levels indicate accelerated biological aging and are implicated in the pathogenesis of colorectal cancer[J].Clin Cancer Res,2011,17(17):5573-5581.
[6]Riegert-Johnson DL,Boardman LA,Crook JE,et al.Shorter peripheral blood telomeres are a potential biomarker for patients with advanced colorectal adenomas[J].Int J Biol Markers,2012,27(4):e375-380.
[7]Dei CA,Spigoni V,Franzini L,et al.Lower endothelial progenitor cell number,family history of cardiovascular disease and reduced HDL-cholesterol levels are associated with shorter leukocyte telomere length in healthy young adults[J].Nutr Metab Cardiovasc Dis,2013,23(3):272-278.
[8]Wu Y,Cui W,Zhang D,et al.The shortening of leukocyte telomere length relates to DNA hypermethylation of LINE-1 in type 2 diabetes mellitus[J].Oncotarget,2017,8(43):73964-73973.
[9]Ma D,Zhu W,Hu S,et al.Association between oxidative stress and telomere length in Type 1 and Type 2 diabetic patients[J].J Endocrinol Invest,2013,36(11):1032-1037.
[10]Shen Q,Zhao X,Yu L,et al.Association of leukocyte telomere length with type 2 diabetes in mainland Chinese populations[J].JClin Endocrinol Metab,2012,97(4):1371-1374.
[11]Gallicchio L,Gadalla SM,Murphy JD,et al.The Effect of Cancer Treatments on Telomere Length:A Systematic Review of the Literature[J].J Natl Cancer Inst,2018,110(10):1048-1058.
[12]Fyhrquist F,Silventoinen K,Saijonmaa O,et al.Telomere length and cardiovascular risk in hypertensive patients with left ventricular hypertrophy:the LIFE study[J].J Hum Hypertens,2011,25(12):711-718.
[13]Wang YY,Chen AF,Wang HZ,et al.Association of shorter mean telomere length with large artery stiffness in patients with coronary heart disease[J].Aging Male,2011,14(1):27-32.
[14]Fan HC,Chen CM,Chi CS,et al.Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma[J].Int J Mol Sci,2019,20(1):200-221.
[15]Arsenis NC,You T,Ogawa EF,et al.Physical activity and telomere length:Impact of aging and potential mechanisms of action[J].Oncotarget,2017,8(27):45008-45019.
[16]Bauman AE,Smith BJ.Healthy ageing:what role can physical activity play?[J].Med J Aust,2000,173(2):88-90.
[17]Hafstad AD,Boardman NT,Lund J,et al.High intensity interval training alters substrate utilization and reduces oxygen consumption in the heart[J].J Appl Physiol(1985),2011,111(5):1235-1241.
[18]Kemi OJ,Loennechen JP,Wislff U,et al.Intensity-controlled treadmill running in mice:cardiac and skeletal muscle hypertrophy[J].JAppl Physiol(1985),2002,93(4):1301-1309.
[19]Sies H,Berndt C,Jones DP,et al.Oxidative Stress[J].Annu Rev Biochem,2017,86:715-748.
[20]Maes M,Galecki P,Chang YS,et al.A review on the oxidative and nitrosative stress(O&NS)pathways in major depression and their possible contribution to the(neuro)degenerative processes in that illness[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(3):676-692.
[21]Borgstahl GEO,Oberley-Deegan RE.Superoxide Dismutases(SODs)and SOD Mimetics[J].Antioxidants(Basel),2018,7(11):156-159.
[22]Glorieux C,Calderon PB.Catalase,a remarkable enzyme:targeting the oldest antioxidant enzyme to find a new cancer treatment approach[J].Biol Chem,2017,398(10):1095-1108.
[23]Schmitt B1,Vicenzi M2,Garrel C3,et al.Effects of N-acetylcysteine,oral glutathione(GSH)and a novel sublingual form of GSH on oxidative stress markers:A comparative crossover study[J].Redox Biol,2015,6:198-205.
[24]Dabrowska N,Wiczkowski A.Analytics of oxidative stress markers in the early diagnosis of oxygen DNA damage[J].Adv Clin Exp Med,2017,26(1):155-166.
[25]Tian F,Tong TJ,Zhang ZY,et al.Age-dependent down-regulation of mitochondrial 8-oxoguanine DNA glycosylase in SAM-P/8 mouse brain and its effect on brain aging[J].Rejuvenation Res,2009,12(3):209-215.
[26]Zheng J,Bizzozero OA.Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion[J].Free Radic Res,2010,44(3):258-266.
[27]Ayala A,Mu1oz MF,Argüelles S.Lipid peroxidation:production,metabolism,and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal[J].Oxid Med Cell Longev,2014,2014:360438.
[28]Roberts LJ,Morrow JD.Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo[J].Free Radic Biol Med,2000,28(4):505-513.