线粒体营养素对运动性疲劳的预防和保护作用及其机制的研究
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摘要
运动性疲劳是训练中一种正常的生理现象。适当的疲劳与快速的恢复是提高运动能力的关键。实验证据表明,运动性疲劳可能是细胞内线粒体自由基过量生成导致细胞氧化损伤的结果。因而,抑制氧化损伤,提高线粒体功能,可能会减少运动性疲劳并促进其快速恢复。在前期研究中,我们将一类靶向于线粒体、促进和维持线粒体结构功能完整的营养物质定义为线粒体营养素。我们的研究提示,选择适当的线粒体营养素,使之分别作用于改善线粒体结构与功能的各条途径,充分发挥多种营养素的协同作用,可能是减少运动性疲劳发生,促进其快速恢复的新的有效手段。
研究目的：
本研究以运动性疲劳进程中线粒体氧化损伤为中心,揭示线粒体营养素或其他抗氧化活性物质—线粒体—运动性疲劳之间的相互关系及其分子机制,研究线粒体损伤中的线粒体数目及合成与分解,和功能的变化；线粒体合成的基因变化；线粒体内膜上的解偶联蛋白的调控。应用多个营养素及抗氧化活性物质在多个模型上筛选及优化组合,确定线粒体营养素及抗氧化活性物质最佳配方,研究结果将为运动性疲劳的营养调控制提供新的理论依据和应用思路。
研究方法：
比较待测营养素——线粒体营养素对力竭运动大鼠模型预防和治疗的效果。建立力竭运动大鼠模型；检测大鼠的各组血乳酸,睾酮,皮质酮等水平。然后将各组大鼠处死,取血,取骨骼肌、心肌,肝脏等组织,抽提骨骼肌,肝脏线粒体,线粒体测定ROS等高活性代谢分子的水平,测定线粒体膜蛋白巯基含量,测定骨骼肌、肝脏线粒体呼吸链活性以及蛋白、核酸及脂质氧化损伤水平；电镜观察线粒体结构。
研究结果：
1)运动距离测试：营养素干预组较力竭运动组的运动距离明显增加；
2)血液指标测试：跑台运动8周后,营养素干预组的谷丙转氨酶含量,血清尿素氮,肌酐含量,红细胞数,血红蛋白的含量均降低；
3)免疫系统测试：营养素干预组细胞凋亡率和活性氧的产生下降；脾淋巴细胞增殖明显增加；
4)抗氧化能力测试：营养素干预组血清总抗氧化力和GST酶活力显著增加；
5)对骨骼肌系统的研究：营养素干预组大鼠骨骼肌的单侧腓肠肌指数,股四头肌指数及比目鱼肌指数均上升,血清肌酸激酶和乳酸脱氢酶的活力下降；肌糖原的含量增加；线粒体数目增加。营养素干预组可显著增加线粒体复合物Ⅰ,Ⅱ和Ⅲ蛋白的表达,促进线粒体DNA的合成,同时上调了参与调控线粒体生成的转录因子PPARGCIA, Nrf1和Tfam的表达;营养素干预可显著上调MFN1和MFN2的表达；
6)对肝脏系统的测试：力竭运动增加肝脏线粒体复合物工,Ⅰ,Ⅳ和Ⅴ的活性,同时增加谷胱甘肽的水平。力竭运动诱导增加肝脏匀浆中丙二醛,谷胱甘肽转移酶,烟酰胺腺嘌呤二核苷酸磷酸辅酶氧化还原酶的能力。营养素干预组能缓解复合物V和NQO-1的能力。同时增加了线粒体复合物Ⅰ和复合物Ⅳ的活性。
结论：
营养素干预可显著提高大鼠的运动能力；增强机体的抗疲劳能力；增强机体的免疫功能；保护机体细胞免受运动性损伤；促进骨骼肌的线粒体生成,缓解肝脏线粒体氧化损伤,改善线粒体的功能。
总之,本研究中所使用的线粒体营养素组合具有优异的抗疲劳,改善线粒体功能的效果。
Endurance exercise-induced fatigue is a common physiological response. The key point for improving exercise ability is having appropriate fatigue with quick recovery. It has been proven that the exercise-induced fatigue could result in over production of reactive oxygen species from mitochondria. Therefore, inhibiting oxidative damage and improving mitochondrial function might be a good strategy to reduce exercise induced-fatigue and accelerate recovery. We have identified a group of nutrients as mitochondrial targeting nutrients because they protect mitochondria from damage and maintain the function of mitochondria for normal physiological activities. In the present study, we have shown that an appropriately selected combination of mitochondrial nutrients is effective on reducing exercise-induced fatigue and accelerating recovery by synergistically improving mitochondrial structure and function through the actions on various pathways.
Aims:Exhaustive exercise causes fatigue due to mitochondrial dysfunction and oxidative stress. In order to find an effective strategy to prevent fatigue and/or enhance recovery, we studied the effects of a combination of mitochondrial targeting nutrients on physical activity, mitochondrial function and oxidative stress in exhaustively exercised rats.
Main methods:The present study was to investigate the effects of a combination of mitochondrial nutrients on physical performance and related biochemical parameters in rats during long-term exhaustive exercise. Rats were randomly divided into three groups:sedentary control (SC), exhaustive-exercise (EC) and exhaustive-exercise with nutrients (EN) which received a combination of mitochondrial nutrients supplementation for 12 weeks (4 week prior to the exercise program and 8 weeks during the exercise prohram). Rats in EC and EN groups were submitted to an exercise program, which contains four- week endurance training and four-week exhaustive exercise.
Key findings:Examination of running distance over the 4-week period revealed that EC group rats ran less distance throughout the entire duration of the exhaustive exercise period compared with EN group rats. The activities of plasma alanine transaminase (ALT), lactate dehydrogenase (LDH) and creatine-kinase (CK) in the EC group were significantly higher than those in the SC group. However, nutrients supplementation attenuated the elevation of these enzyme activities in the plasma of rats. The rise in malondialdehyde (MDA) following the treadmill test was significantly less after nutrients supplementation. In addition, nutrients also inhibited the decrease of the activity of glutathione S-transferase (GST) and total antioxidant capacity (TOC) in plasma. The percentage of apoptotic cells increased significantly in spleen lympocytes and the generation of reactive oxygen species (ROS) also enhanced after 24h-recovery of the exhaustive exercise in the EC group. Nutrients supplementation also suppressed the elevation of ROS and apoptosis in the EN group. We found that the nutrient treatment significantly increased the running time, improved mitochondrial function and reduced oxidative stress in muscle.
We also found that exhaustive exercise induced an increase in activities of mitochondrial complexes I, IV and V, an increase in GSH level and a decrease in ROS in liver mitochondria but no change in levels of ROS and MDA, or in activities of complexes II and III. Exercise also induced a significant increase in MDA and activities of glutathione S-transferase and NADPH-quinone-oxidoreductase 1 (NQO-1) in the liver homogenate. The nutrient treatment showed amelioration of the complex V and NQO-1 activities, but no effect on other parameters.
Conclusions:We found that exhaustive exercise reduced the running time, increased the activities of ALT and LDH and the levels of red blood cells, hemoglobin and hemocrit, depressed kidney function (decreased levels of BUN and creatine) and immune function, decreased mitochondrial function in muscle and liver, elevated oxidative stress and decreased antioxidant defense in plasma, muscle, liver and spleen. We also found that the mitochondrial targeting nutrient treatment treatment significantly increased the running time, ameliorated the abnormality of plasma enzymes and oxygen transportation system, imporved the kidney function and immune function, protected the mitochondrial dysfunction in muscle and liver, enhanced antioxidant defense system and reduced oxidative stress in plasma, muscle, liver and spleen. In addition, we showed that, the nutrient treatment has less impact on exercise-induced oxidative and mitochondrial stress in the liver than in the muscle.
研究目的：
本研究以运动性疲劳进程中线粒体氧化损伤为中心,揭示线粒体营养素或其他抗氧化活性物质—线粒体—运动性疲劳之间的相互关系及其分子机制,研究线粒体损伤中的线粒体数目及合成与分解,和功能的变化；线粒体合成的基因变化；线粒体内膜上的解偶联蛋白的调控。应用多个营养素及抗氧化活性物质在多个模型上筛选及优化组合,确定线粒体营养素及抗氧化活性物质最佳配方,研究结果将为运动性疲劳的营养调控制提供新的理论依据和应用思路。
研究方法：
比较待测营养素——线粒体营养素对力竭运动大鼠模型预防和治疗的效果。建立力竭运动大鼠模型；检测大鼠的各组血乳酸,睾酮,皮质酮等水平。然后将各组大鼠处死,取血,取骨骼肌、心肌,肝脏等组织,抽提骨骼肌,肝脏线粒体,线粒体测定ROS等高活性代谢分子的水平,测定线粒体膜蛋白巯基含量,测定骨骼肌、肝脏线粒体呼吸链活性以及蛋白、核酸及脂质氧化损伤水平；电镜观察线粒体结构。
研究结果：
1)运动距离测试：营养素干预组较力竭运动组的运动距离明显增加；
2)血液指标测试：跑台运动8周后,营养素干预组的谷丙转氨酶含量,血清尿素氮,肌酐含量,红细胞数,血红蛋白的含量均降低；
3)免疫系统测试：营养素干预组细胞凋亡率和活性氧的产生下降；脾淋巴细胞增殖明显增加；
4)抗氧化能力测试：营养素干预组血清总抗氧化力和GST酶活力显著增加；
5)对骨骼肌系统的研究：营养素干预组大鼠骨骼肌的单侧腓肠肌指数,股四头肌指数及比目鱼肌指数均上升,血清肌酸激酶和乳酸脱氢酶的活力下降；肌糖原的含量增加；线粒体数目增加。营养素干预组可显著增加线粒体复合物Ⅰ,Ⅱ和Ⅲ蛋白的表达,促进线粒体DNA的合成,同时上调了参与调控线粒体生成的转录因子PPARGCIA, Nrf1和Tfam的表达;营养素干预可显著上调MFN1和MFN2的表达；
6)对肝脏系统的测试：力竭运动增加肝脏线粒体复合物工,Ⅰ,Ⅳ和Ⅴ的活性,同时增加谷胱甘肽的水平。力竭运动诱导增加肝脏匀浆中丙二醛,谷胱甘肽转移酶,烟酰胺腺嘌呤二核苷酸磷酸辅酶氧化还原酶的能力。营养素干预组能缓解复合物V和NQO-1的能力。同时增加了线粒体复合物Ⅰ和复合物Ⅳ的活性。
结论：
营养素干预可显著提高大鼠的运动能力；增强机体的抗疲劳能力；增强机体的免疫功能；保护机体细胞免受运动性损伤；促进骨骼肌的线粒体生成,缓解肝脏线粒体氧化损伤,改善线粒体的功能。
总之,本研究中所使用的线粒体营养素组合具有优异的抗疲劳,改善线粒体功能的效果。
Endurance exercise-induced fatigue is a common physiological response. The key point for improving exercise ability is having appropriate fatigue with quick recovery. It has been proven that the exercise-induced fatigue could result in over production of reactive oxygen species from mitochondria. Therefore, inhibiting oxidative damage and improving mitochondrial function might be a good strategy to reduce exercise induced-fatigue and accelerate recovery. We have identified a group of nutrients as mitochondrial targeting nutrients because they protect mitochondria from damage and maintain the function of mitochondria for normal physiological activities. In the present study, we have shown that an appropriately selected combination of mitochondrial nutrients is effective on reducing exercise-induced fatigue and accelerating recovery by synergistically improving mitochondrial structure and function through the actions on various pathways.
Aims:Exhaustive exercise causes fatigue due to mitochondrial dysfunction and oxidative stress. In order to find an effective strategy to prevent fatigue and/or enhance recovery, we studied the effects of a combination of mitochondrial targeting nutrients on physical activity, mitochondrial function and oxidative stress in exhaustively exercised rats.
Main methods:The present study was to investigate the effects of a combination of mitochondrial nutrients on physical performance and related biochemical parameters in rats during long-term exhaustive exercise. Rats were randomly divided into three groups:sedentary control (SC), exhaustive-exercise (EC) and exhaustive-exercise with nutrients (EN) which received a combination of mitochondrial nutrients supplementation for 12 weeks (4 week prior to the exercise program and 8 weeks during the exercise prohram). Rats in EC and EN groups were submitted to an exercise program, which contains four- week endurance training and four-week exhaustive exercise.
Key findings:Examination of running distance over the 4-week period revealed that EC group rats ran less distance throughout the entire duration of the exhaustive exercise period compared with EN group rats. The activities of plasma alanine transaminase (ALT), lactate dehydrogenase (LDH) and creatine-kinase (CK) in the EC group were significantly higher than those in the SC group. However, nutrients supplementation attenuated the elevation of these enzyme activities in the plasma of rats. The rise in malondialdehyde (MDA) following the treadmill test was significantly less after nutrients supplementation. In addition, nutrients also inhibited the decrease of the activity of glutathione S-transferase (GST) and total antioxidant capacity (TOC) in plasma. The percentage of apoptotic cells increased significantly in spleen lympocytes and the generation of reactive oxygen species (ROS) also enhanced after 24h-recovery of the exhaustive exercise in the EC group. Nutrients supplementation also suppressed the elevation of ROS and apoptosis in the EN group. We found that the nutrient treatment significantly increased the running time, improved mitochondrial function and reduced oxidative stress in muscle.
We also found that exhaustive exercise induced an increase in activities of mitochondrial complexes I, IV and V, an increase in GSH level and a decrease in ROS in liver mitochondria but no change in levels of ROS and MDA, or in activities of complexes II and III. Exercise also induced a significant increase in MDA and activities of glutathione S-transferase and NADPH-quinone-oxidoreductase 1 (NQO-1) in the liver homogenate. The nutrient treatment showed amelioration of the complex V and NQO-1 activities, but no effect on other parameters.
Conclusions:We found that exhaustive exercise reduced the running time, increased the activities of ALT and LDH and the levels of red blood cells, hemoglobin and hemocrit, depressed kidney function (decreased levels of BUN and creatine) and immune function, decreased mitochondrial function in muscle and liver, elevated oxidative stress and decreased antioxidant defense in plasma, muscle, liver and spleen. We also found that the mitochondrial targeting nutrient treatment treatment significantly increased the running time, ameliorated the abnormality of plasma enzymes and oxygen transportation system, imporved the kidney function and immune function, protected the mitochondrial dysfunction in muscle and liver, enhanced antioxidant defense system and reduced oxidative stress in plasma, muscle, liver and spleen. In addition, we showed that, the nutrient treatment has less impact on exercise-induced oxidative and mitochondrial stress in the liver than in the muscle.
引文
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