有氧运动对2型糖尿病大鼠AGE-RAGE轴及NF-κB通路的影响
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摘要
目的研究有氧运动对2型糖尿病(T2DM)大鼠AGE-RAGE轴及NF-κB通路的影响,探讨T2DM运动康复作用.方法 8周龄雄性Wister大鼠高糖高脂饮食后,应用链脲佐菌素诱导建立T2DM大鼠.将30只造模成功的T2DM大鼠随机分成3组(n=10):T2DM组、T2DM加低强度运动组(T2DML)和T2DM加中强度运动组(T2DMM).运动组实施运动方案.采用ELISA法分别测定实验大鼠血浆、骨骼肌和心肌的晚期糖基化终产物(AGEs)及其受体(RAGE)和核因子κB(NF-κB)水平.结果与T2DM组相比,T2DML组血、骨骼肌和心肌的NF-κB水平显著下降(P<0.05);T2DMM组血、骨骼肌和心肌的AGEs、RAGE和NF-κB水平均显著下降(P<0.05);与T2DML组相比,T2DMM组血、骨骼肌和心肌的NF-κB水平均显著下降(P<0.05).结论中强度有氧运动能抑制AGE-RAGE轴和NF-κB通路,降低T2DM氧化应激和炎症反应,减轻组织损伤,对T2DM及其并发症具有防治作用.
Objective The aim of this study was to evaluate the effects of aerobic exercise on AGE-RAGE axis and nuclear factor kappa B pathway in type 2 diabete rats and to discuss the rehabilitation function of aerobic exercise in type 2 diabetes mellitus(T2DM). Methods After the 8-week-old male Wistar rats were fed with a high sugar and high fat for 4 weeks, type 2 diabetes rats were induced by streptozotocin way. 30 type 2 diabetes rats were allocated at random into 3 groups: type 2 diabetes mellitus(T2DM), low-and moderate-intensity exercise groups(T2DML,T2DMM). Exercise group performed exercise protocol respectively. The AGEs, RAGE and NF-κB levels of the blood,muscle and heart were detected by ELISA method respectively. Results Compared with T2DM group, the NF-κB level of the blood, muscle and heart were decreased in T2DML group significantly(P<0.05);the AGEs, RAGE and NF-κB level of the blood, muscle and heart were decreased in T2DMM group significantly(P<0.05). Compared with T2DML group, the NF-κB level of the blood, muscle and heart were decreased in T2DMM group significantly(P<0.05). Conclusion Moderate intensity aerobic exercise inhibits AGE-RAGE axis and NF-κB pathway, which may decrease oxidative stress and inflammation, and so reduce tissue injure for the prevention and treatment of complications of the T2DM.
Objective The aim of this study was to evaluate the effects of aerobic exercise on AGE-RAGE axis and nuclear factor kappa B pathway in type 2 diabete rats and to discuss the rehabilitation function of aerobic exercise in type 2 diabetes mellitus(T2DM). Methods After the 8-week-old male Wistar rats were fed with a high sugar and high fat for 4 weeks, type 2 diabetes rats were induced by streptozotocin way. 30 type 2 diabetes rats were allocated at random into 3 groups: type 2 diabetes mellitus(T2DM), low-and moderate-intensity exercise groups(T2DML,T2DMM). Exercise group performed exercise protocol respectively. The AGEs, RAGE and NF-κB levels of the blood,muscle and heart were detected by ELISA method respectively. Results Compared with T2DM group, the NF-κB level of the blood, muscle and heart were decreased in T2DML group significantly(P<0.05);the AGEs, RAGE and NF-κB level of the blood, muscle and heart were decreased in T2DMM group significantly(P<0.05). Compared with T2DML group, the NF-κB level of the blood, muscle and heart were decreased in T2DMM group significantly(P<0.05). Conclusion Moderate intensity aerobic exercise inhibits AGE-RAGE axis and NF-κB pathway, which may decrease oxidative stress and inflammation, and so reduce tissue injure for the prevention and treatment of complications of the T2DM.
引文
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[9]STIRBAN A,GAWLOWSKI T,RODEN M.Vascular effects of advanced glycationendproducts:clinical effects and molecular mechanisms[J].Mol Metab,2013,3(2):94-108.
[10]EVANS J L,GOLDFINE I D,MADDUX B A,et al.Oxidative stress and stress-activated signaling pathways:A unifying hypothesis of type 2 diabetes[J].Endocr Rev,2002,23(5):599-622.
[11]YAMAMOTO Y,GAYNOR R B.Role of the NF-kappa B pathway in the pathogenesis of human disease states[J].Curr Mol Med,2001,1(3):287-296.
[12]FUKAMI K,YAMAGISHI S,OKUDA S.Role of AGEsRAGE system in cardiovascular disease[J].Curr Pharm Des,2014,20(14):2395-2402.
[13]沈志祥,刘翠鲜,郑洁皎,等.有氧运动对2型糖尿病大鼠血浆晚期糖基化终产物的影响[J].中华物理医学与康复杂志,2011,33(3):167-170.
[14]TEIXEIRA-LEMOS E,NUNES S,TEIXEIRA F,et al.Regular physical exercise training assists in preventing type2 diabetes development:focus on its antioxidant and anti-inflammatory properties[J].Cardiovasc Diabetol,2011,10(1):1-15.
[15]SRIWIJITKAMOL A,CHRIST-ROBERTS C,BERRIA R,et al.Reduced skeletal muscle inhibitor of kappa B beta content is associated with insulin resistance in subjects with type 2 diabetes[J].Diabetes,2006,55(4):760-767.
[2]李爱卿,王志慧,赵跃武.高糖高脂饲料诱导Ⅱ型糖尿病大鼠模型[J].临床医药实践杂志,2005,14(2):130-131.
[3]BOOTH FW,LAYE M J,SPANGENBURG E E.Gold standards for scientists who are conducting animal-based exercise studies[J].J Appl Physiol,2010,108(1):219-221.
[4]POWERS S K,SMUDER A J,KAVAZIS A N,et al.Experimental guidelines for studies designed to investigate the impact of antioxidant supplementation on exercise performance[J].Int J Sport Nutr Exerc Metab,2010,20(1):2-14.
[5]BEDFORD T G,TIPTON C M,WILSON N C,et al.Maximum oxygen consumption of rats and its changes with various experimental procedures[J].J Appl Physiol,1979,47(6):1278-1283.
[6]COPP S W,HAGEMAN K S,BEHNKE B J,et al.Effects of Type II diabetes on exercising skeletal muscle blood flow in the rat[J].J Appl Physiol,2010,109(6):1347-1353.
[7]DE LEMOS E T,REIS F,BAPTISTA S,et al.Exercise training is associated with improved levels of C-reactive protein and adiponectin in ZDF(type 2)diabetic rats[J].Med Sci Monit,2007,13(8):168-174.
[8]YAMAGISHI S,FUKAMI K,MATSUI T.Crosstalk between advanced glycation end products(AGEs)-receptor RAGE axis and dipeptidyl peptidase-4-incretin system in diabetic vascular complications[J].Cardiovasc Diabetol,2015,14(2):176-187.
[9]STIRBAN A,GAWLOWSKI T,RODEN M.Vascular effects of advanced glycationendproducts:clinical effects and molecular mechanisms[J].Mol Metab,2013,3(2):94-108.
[10]EVANS J L,GOLDFINE I D,MADDUX B A,et al.Oxidative stress and stress-activated signaling pathways:A unifying hypothesis of type 2 diabetes[J].Endocr Rev,2002,23(5):599-622.
[11]YAMAMOTO Y,GAYNOR R B.Role of the NF-kappa B pathway in the pathogenesis of human disease states[J].Curr Mol Med,2001,1(3):287-296.
[12]FUKAMI K,YAMAGISHI S,OKUDA S.Role of AGEsRAGE system in cardiovascular disease[J].Curr Pharm Des,2014,20(14):2395-2402.
[13]沈志祥,刘翠鲜,郑洁皎,等.有氧运动对2型糖尿病大鼠血浆晚期糖基化终产物的影响[J].中华物理医学与康复杂志,2011,33(3):167-170.
[14]TEIXEIRA-LEMOS E,NUNES S,TEIXEIRA F,et al.Regular physical exercise training assists in preventing type2 diabetes development:focus on its antioxidant and anti-inflammatory properties[J].Cardiovasc Diabetol,2011,10(1):1-15.
[15]SRIWIJITKAMOL A,CHRIST-ROBERTS C,BERRIA R,et al.Reduced skeletal muscle inhibitor of kappa B beta content is associated with insulin resistance in subjects with type 2 diabetes[J].Diabetes,2006,55(4):760-767.