姜黄素对过度训练大鼠骨骼肌p38 MAPK的表达及抗氧化能力的影响
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摘要
目的:观察姜黄素对过度训练大鼠骨骼肌p38 MAPK磷酸化及氧化应激的影响,探讨姜黄素对骨骼肌损伤的保护作用及机制。方法:以负荷游泳训练的方法创建大强度耐力训练的大鼠模型,以等量负荷有氧运动训练大鼠为实验对照,经42天负荷游泳训练后,检测各组大鼠骨骼肌组织中p38 MAPK mRNA和蛋白的表达、超氧化物歧化酶(superoxide dismutase,SOD)的活性、丙二醛(malondialdehyde,MDA)含量,并检测血清肌酸激酶(creatine kinase,CK)活性和乳酸脱氢酶(lactate dehydrogenase,LDH)活性。结果:1)与对照组比较,过度训练使大鼠骨骼肌SOD活性显著降低(P<0.05),而姜黄素处理后则可使过度训练大鼠骨骼肌的SOD活性显著升高(P<0.05);2)过度训练组大鼠的骨骼肌MDA含量较空白对照组和有氧训练组升高(P<0.05),而与过度训练组比较,姜黄素+过度训练组大鼠的骨骼肌MDA含量则降低(P<0.05);3)与对照组比较,血清CK和LDH活性在过度训练组明显升高,而与过度训练组比较,姜黄素+过度训练组大鼠骨骼肌的CK和LDH的活性则下降(P<0.05);4) qRT-PCR和Western blotting检测发现,与对照组比较,过度训练组大鼠骨骼肌组织p38 MAPK mRNA和蛋白的表达上调(P<0.05),而与过度训练组比较,姜黄素+过度训练组大鼠骨骼肌组织p38 MAPK mRNA和蛋白的表达则下调(P<0.05)。结论:过度训练可使大鼠p38 MAPK信号通路蛋白过度表达,并引起骨骼肌氧化应激损伤,而姜黄素则可抑制p38 MAPK信号通路蛋白的表达,提高骨骼肌抗氧化能力,抑制骨骼肌纤维的损伤,从而预防和延缓过度训练所致的大鼠骨骼肌氧化应激损伤及运动疲劳的发生与发展。
Objective: To observe effects of curcumin on the p38 MAPK phosphorylation and oxidative stress in over-trained skeletal muscle, and explore the protective mechanism of curcumin on the injured muscle. Methods: A rat model of high intensity endurance training was established by exhaustive swimming. The control group was the equivalent load aerobic training rat model. After load swimming training for 42 days, p38 MAPK expression, activity of superoxide dismutase(SOD), content of malondialdehyde(MDA), activity of creatine kinase(CK),and lactate dehydrogenase(LDH) was detected in the rat skeletal muscle. Result: 1) Compared with the control, the SOD activity was obviously decreased in the overtraining group(P< 0.05)and increased by curcumin treated(P< 0.05). 2) MDA content of skeletal muscle was increased in overtraining group, compared with the control group and aerobic training group(P< 0.05).Compared with overtraining group, the MDA content decreased in the overtraining rat treated with curcumin(P< 0.05). 3) Compared with control group, activity of CK and LDH was apparently increased in overtraining group. While compared with overtraining group, the activity of CK and LDH was decreased in the overtraining rat treated with curcumin(P< 0.05). 4) p38 MAPK mRNA and protein expression upregulated in overtraining group, compared with control group(P< 0.05); while the expression of p38 MAPK downregulated in the overtraining rat treated with curcumin, compared with the overtraining rat(P< 0.05). Conclusion: Overtraining results in the overexpression of p38 MAPK and induces the oxidative stress injury in skeletal muscle of rat. Curcumin enhances the capacity of antioxidative damage and reduces the damage of the skeletal muscle ?ber through inhibiting the p38 MAPK signal pathway. Thus curcumin prevent and delay the oxidative stress injury of the rat skeletal muscle and the development of exercise-induced fatigue.
Objective: To observe effects of curcumin on the p38 MAPK phosphorylation and oxidative stress in over-trained skeletal muscle, and explore the protective mechanism of curcumin on the injured muscle. Methods: A rat model of high intensity endurance training was established by exhaustive swimming. The control group was the equivalent load aerobic training rat model. After load swimming training for 42 days, p38 MAPK expression, activity of superoxide dismutase(SOD), content of malondialdehyde(MDA), activity of creatine kinase(CK),and lactate dehydrogenase(LDH) was detected in the rat skeletal muscle. Result: 1) Compared with the control, the SOD activity was obviously decreased in the overtraining group(P< 0.05)and increased by curcumin treated(P< 0.05). 2) MDA content of skeletal muscle was increased in overtraining group, compared with the control group and aerobic training group(P< 0.05).Compared with overtraining group, the MDA content decreased in the overtraining rat treated with curcumin(P< 0.05). 3) Compared with control group, activity of CK and LDH was apparently increased in overtraining group. While compared with overtraining group, the activity of CK and LDH was decreased in the overtraining rat treated with curcumin(P< 0.05). 4) p38 MAPK mRNA and protein expression upregulated in overtraining group, compared with control group(P< 0.05); while the expression of p38 MAPK downregulated in the overtraining rat treated with curcumin, compared with the overtraining rat(P< 0.05). Conclusion: Overtraining results in the overexpression of p38 MAPK and induces the oxidative stress injury in skeletal muscle of rat. Curcumin enhances the capacity of antioxidative damage and reduces the damage of the skeletal muscle ?ber through inhibiting the p38 MAPK signal pathway. Thus curcumin prevent and delay the oxidative stress injury of the rat skeletal muscle and the development of exercise-induced fatigue.
引文
常波,赵大林,官一鹏,等,2014.过度训练对大鼠骨骼肌自由基代谢和MAPK信号通路ERK磷酸化蛋白表达的影响[C].2014年中国运动生理生化学术会议论文集,37.
池爱平,熊正英,陈锦屏,2006.补充不同剂量姜黄素对运动大鼠心肌和骨骼肌组织自由基损伤及力竭运动时间的影响[J].中国运动医学杂志,25(3):342-343.
崔笑梅,曹建民,周海涛,等,2017.黑果枸杞子对过度训练大鼠骨骼肌MAPK信号通道蛋白表达及抗氧化应激损伤能力的影响[J].中国实验方剂学杂志,23(3):122-127.
高超,刘阳,赵佳,等,2017.姜黄素对急性游泳训练小鼠骨骼肌损伤的保护作用[J].中国食物与营养,23(6):54-58.
李琳燕,2011.过度训练对大鼠骨骼肌自由基代谢和MAPK信号通路p38蛋白表达的影响[J].沈阳体育学院学报,30(1):62-64.
魏连波,黄燕峰,2015.姜黄素促进C2C12骨骼肌细胞增殖分化及其机制研究[C].中国中西医结合学会肾脏疾病专业委员会2015年学术年会资料汇编,616.
吴珊,万津,陈代文,等,2016.姜黄素和亮氨酸对免疫应激大鼠骨骼肌蛋白质降解的缓解效应[J].营养学报,38(1):19-23.
肖卫华,陈佩杰,2014.过度训练对骨骼肌生长及相关基因表达的影响[C].2014年中国运动生理生化学术会议论文集,123-124.
郑佳,闻颖,2013.姜黄素与炎症诱导的肥胖、糖尿病关系的研究进展[J].预防医学情报杂志,29(9):804-807.
周瑶瑶,韦小未,郭玲玉,等,2016.姜黄素对脂多糖联合干扰素γ诱导的巨噬细胞炎症因子表达的影响及其机制[J].中国动脉硬化杂志,24(1):44-48.
GANDRA P G,VALENTE R H,PERALES J,et al.,2012.Proteomic profiling of skeletal muscle in an animal model of overtraining[J].Proteomics,12(17):2663-2667.
JIN H,QIAO F,WANG Y,et al.,2015.Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway[J].Oncol Rep,34(5):2782-2789.
MARTINEZ P F,BONOMO C,GUIZONI D M,et al.,2016,Modulation of MAPK and NF-954;b signaling pathways by antioxidant therapy in skeletal muscle of heart failure[J].RatsCell Physiol Biochem,39(1):371-384.
MERRY T L,RISTOW M,2016.Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?[J].J Physiol,594(18):5135-5147.
NAGAHAMA K,KUMANO T,OYAMA N,et al.,2015.Curcumisome nanovesicles generated by self-assembly of curcumin amphiphiles toward cancer theranostics[J].Biomater Sci,3(12):1566-1578.
PEREIRA B C,PAULI J R,ANTUNES L M,et al.,2013.Overtraining is associated with DNA damage in blood and skeletal muscle cells of Swiss mice[J].BMC Physiol,(13):11.
SHILL D D,SOUTHEM W M,WILLINGHAM T B,et al.,2016.Mitochondria-specific antioxidant supplementation does not influence endurance exercise training-induced adaptations in circulating angiogenic cells,skeletal muscle oxidative capacity or maximal oxygen uptake[J].J Physiol,594(23):7005-7014.
池爱平,熊正英,陈锦屏,2006.补充不同剂量姜黄素对运动大鼠心肌和骨骼肌组织自由基损伤及力竭运动时间的影响[J].中国运动医学杂志,25(3):342-343.
崔笑梅,曹建民,周海涛,等,2017.黑果枸杞子对过度训练大鼠骨骼肌MAPK信号通道蛋白表达及抗氧化应激损伤能力的影响[J].中国实验方剂学杂志,23(3):122-127.
高超,刘阳,赵佳,等,2017.姜黄素对急性游泳训练小鼠骨骼肌损伤的保护作用[J].中国食物与营养,23(6):54-58.
李琳燕,2011.过度训练对大鼠骨骼肌自由基代谢和MAPK信号通路p38蛋白表达的影响[J].沈阳体育学院学报,30(1):62-64.
魏连波,黄燕峰,2015.姜黄素促进C2C12骨骼肌细胞增殖分化及其机制研究[C].中国中西医结合学会肾脏疾病专业委员会2015年学术年会资料汇编,616.
吴珊,万津,陈代文,等,2016.姜黄素和亮氨酸对免疫应激大鼠骨骼肌蛋白质降解的缓解效应[J].营养学报,38(1):19-23.
肖卫华,陈佩杰,2014.过度训练对骨骼肌生长及相关基因表达的影响[C].2014年中国运动生理生化学术会议论文集,123-124.
郑佳,闻颖,2013.姜黄素与炎症诱导的肥胖、糖尿病关系的研究进展[J].预防医学情报杂志,29(9):804-807.
周瑶瑶,韦小未,郭玲玉,等,2016.姜黄素对脂多糖联合干扰素γ诱导的巨噬细胞炎症因子表达的影响及其机制[J].中国动脉硬化杂志,24(1):44-48.
GANDRA P G,VALENTE R H,PERALES J,et al.,2012.Proteomic profiling of skeletal muscle in an animal model of overtraining[J].Proteomics,12(17):2663-2667.
JIN H,QIAO F,WANG Y,et al.,2015.Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway[J].Oncol Rep,34(5):2782-2789.
MARTINEZ P F,BONOMO C,GUIZONI D M,et al.,2016,Modulation of MAPK and NF-954;b signaling pathways by antioxidant therapy in skeletal muscle of heart failure[J].RatsCell Physiol Biochem,39(1):371-384.
MERRY T L,RISTOW M,2016.Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?[J].J Physiol,594(18):5135-5147.
NAGAHAMA K,KUMANO T,OYAMA N,et al.,2015.Curcumisome nanovesicles generated by self-assembly of curcumin amphiphiles toward cancer theranostics[J].Biomater Sci,3(12):1566-1578.
PEREIRA B C,PAULI J R,ANTUNES L M,et al.,2013.Overtraining is associated with DNA damage in blood and skeletal muscle cells of Swiss mice[J].BMC Physiol,(13):11.
SHILL D D,SOUTHEM W M,WILLINGHAM T B,et al.,2016.Mitochondria-specific antioxidant supplementation does not influence endurance exercise training-induced adaptations in circulating angiogenic cells,skeletal muscle oxidative capacity or maximal oxygen uptake[J].J Physiol,594(23):7005-7014.