运动性疲劳对大鼠心肌细胞钙浓度的影响及人参皂苷单体Rb1对心肌保护作用的研究
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摘要
运动性疲劳指机体不能将它的机能保持在某一特定水平,或者不能维持某一预定的运动强度[1]。运动性疲劳对心脏功能影响研究虽然有报道,但其影响作用及机制仍然不清楚,尤其是在分子细胞水平上对心肌细胞内[Ca~(2+)]i的研究没有报道,因此本论文通过游泳训练制备运动性疲劳大鼠模型,检测心肌细胞钙离子浓度的变化,探讨运动性疲劳对心脏功能的影响。本文研究了心肌细胞内[Ca~(2+)]i变化的规律,血液生化,心电,心肌力学相关指标的变化及人参皂苷单体Rb1对心肌的保护作用,这对人们的健康及长期疲劳心肌钙水平调控控制范围具有重要的理论意义和现实意义。
通过连续15天,每天3小时的游泳耐力运动建立大鼠运动性疲劳模型,大鼠疲劳时游泳水淹过鼻,且经常下沉。应用自动生化分析仪器测定血浆乳酸脱氢酶,肌酸磷酸激酶,葡萄糖,Ca~(2+)变化。应用Power Lab测定标Ⅱ导联心电图(ECG),在体左心室收缩压,左室舒张末期压,室内最大升降速率,心率。为了排除神经和体液因素的影响,应用Langendorff离体灌流测定左心室收缩压,左室舒张末期压,室内最大升降速率,心率。并在细胞水平上应用绝对钙离子成像技术测定了心肌细胞[Ca~(2+)]i。
运动性疲劳可使大鼠血浆CK由对照组的357.83±50.45IU/L显著上升至558.1±101.2IU/L (P<0.01),升高55.97%; Glu由对照组的7.63±1.62mmol/L显著升高至10.28±2.08mmol/L (P<0.05),升高34.67%;Ca~(2+)由对照组的2.57±0.05mmol/L显著下降至2.21±0.11mmol/L(P<0.01),降低13.9%。过量运动性疲劳可使大鼠心脏显著增大,引起心肌肥厚,肌结构重组。心脏重量由0.573±0.03g显著增重至疲劳后的1.049±0.08 (P<0.01),增重82.89%运动性疲劳可使大鼠心电R波幅值显著增大,由0.5012±0.05mv增至0.9072±0.3152mv(P<0.01),增幅81.01%。运动性疲劳可使大鼠心肌力学指标较正常大鼠显著升高。在体LVSP显著升高,由15.88±0.47kPa增至18.14±0.19kPa (P<0.01),增幅14.24%;+dp/dt显著升高(P<0.05),增加了45.32%。对离体心脏,LVSP运动性疲劳组(5.681±0.497kPa)显著高于(P<0.01)正常组(4.539±0.389kPa),高出25.17%;+dp/dt显著升高(P<0.05),增加了30.78%。对心肌细胞,运动性疲劳可导致细胞内[Ca~(2+)]i显著升高,由正常的107.77±27.04nM上升至308.58±69.48nM,升高了186.3%。
人参皂苷单体Rb1可使运动性疲劳大鼠血浆CK的升高回复至292±63.89IU/L(P<0.01) ,下降47.68% ; Rb1可使Glu进一步上升至14.85±3.73mmol/L(P<0.05),上升44.46%; Rb1可使运动性疲劳引起的Ca~(2+)下降回升至2.47±0.08mmol/L (P<0.01),回升11.61%。运动性疲劳使大鼠血浆中Ca~(2+)浓度降低,肌细胞内Ca~(2+)增加,Rb1能有效提高血浆中Ca~(2+)浓度,而起到阻滞Ca~(2+)向细胞内流,减缓细胞钙超载的作用。Rb1对运动性疲劳引起的R波幅值降低不明显。人参皂苷单体Rb1可降低运动性疲劳大鼠心肌收缩力,对心肌起到保护作用。Rb1可使运动疲劳引起的LVSP上升回复至16.41±0.43kPa,下降9.53%; Rb1可使+dp/dt升高显著回复(P<0.01),下降了40.34%。对离体心脏,Rb1可极显著的降低运动性疲劳大鼠LVSP(2.737±0.595kPa),降低51.83%;Rb1极显著(P<0.01)的降低了+dp/dt,下降了46.53%。Rb1对正常组心肌也具有负性肌力效应,作用效果不如疲劳组明显。应用Ca~(2+)通道阻滞剂维拉帕米(Varapamil)做阳性对照,对疲劳组心肌也具有与Rb1相似的效果,作用更为明显,但可使心率显著降低。
运动性致疲劳可使大鼠心肌收缩力增强,心脏体积增大,心肌肥厚使得心功能增强,使大鼠血浆中Ca~(2+)浓度降低,心肌细胞内[Ca~(2+)]i升高。Rb1能有效提高血浆中Ca~(2+)浓度,而起到阻滞Ca~(2+)向细胞内流,减缓细胞钙超载的作用,Rb1可降低运动性疲劳大鼠心肌的收缩力,对心肌起到保护作用。
Exercise induced fatigue is body can’t keep its physiological process on an order level or can’t keep on certain sports strength. To study the mechanism of exercise induced fatigue and medical health care support improve the exercise ability and fatigue resume has a very important theory, practice, society benefit for improving exercise achievement and keeping fit. Take the data of [Ca~(2+)]i in myocardial cells, plasma biochemical indices, the apparent of heart, ECG and myocardium mechanics to explore the effect of exercise induced fatigue on rats’heart function. And then study the anti-exercise fatigue function of ginsengnoside Rb1, which can scavenge oxygen free radicals, improve the activity of SOD, block cell calcium channel opening.
The exercise-induced fatigue models in rats were established by 15 days chronic swimming training. Using the automatic biochemical analysis instruments to take the data of plasma biochemical indices; take the standardⅡ-lead ECG; take the data of myocardium mechanics in vivo and vitro; and using the ion imaging technique to measure [Ca~(2+)]i in mycardial cells.
Exercise-induced fatigue made the CK of rats blood plasma increased from 357.83±50.45IU/L to 558.1±101.2IU/L (P<0.01), increased 55.97%; Glu increased from 7.63±1.62mmol/L to 10.28±2.08mmol/L (P<0.05), increased 34.67%; Ca~(2+) decreased from 2.57±0.05mmol/L to 2.21±0.11mmol/L(P<0.01), decreased 13.9%. Exercise-induced fatigue made rats’heart increased obviously and myocardial hypertrophy. The weight of rats’heart increased from 0.573±0.03g to 1.049±0.08 (P<0.01), increased 82.89%. Exercise-induced fatigue made rats’ECG R wave increased rapidly from 0.5012±0.05mv to 0.9072±0.3152mv(P<0.01), increased 81.01%. Exercise-induced fatigue made rats’myocardium mechanics much higher than control. In vivo, exercise- induced fatigue, LVSP increased from 15.88±0.47kPa to 18.14±0.19kPa (P<0.01), increased 14.24%; +dp/dt increased obviously (P<0.05), increased 45.32%. In vitro, LVSP in Exercise-induced fatigue(5.681±0.497kPa) was much higher than control (4.539±0.389kPa, P<0.01), 25.17% higher; +dp/dt increased obviously (P<0.05) in exercise-induced fatigue rats, increased 30.78%. The [Ca~(2+)]i in fatigue myocardial cells (308.58±69.48nM) are much higher than control (107.77±27.04nM).
Ginsengnoside Rb1 can make the CK rise of exercise-induced fatigue rats blood plasma decrease to 292±63.89IU/L(P<0.01), decreased 47.68%; Rb1 can make Glu increased more to 14.85±3.73mmol/L(P<0.05), increased 44.46%; Rb1 can make it recover to 2.47±0.08mmol/L (P<0.01), increased 11.61%. Exercise-induced fatigue can reduce blood plasma Ca~(2+) concentration, enhance in-cell Ca~(2+) concentration, and Rb1 can increase blood plasma Ca~(2+) concentration, decrease in-cell Ca~(2+) concentration, delay cell calcium overload. Rb1 did little to decrease R wave in exercise-induced fatigue rats. Ginsengnoside Rb1 decreased myocardium mechanicals in fatigue rats, and protect cardiac muscle. In vivo, exercise- induced fatigue, Rb1 recovered LVSP to 16.41±0.43kPa(P<0.01), decreased 9.53%; Rb1 also recovered +dp/dt(P<0.01), decreased 40.34%. In vitro, Rb1 can reduce LVSP rapidly to 2.737±0.595kPa (P<0.01), reduced 51.83%; Rb1 decreased +dp/dt rapidly too(P<0.01), decreased 46.53%. Rb1 also has the negative myocardium mechanics in control, but not significant to fatigue. Varapamil has similar effect on fatigue hearts, and more effective, but it reduced heart rate notably.
Exercise-induced fatigue rats have higher myocardium mechanics, bigger heart, and get myocardial hypertrophy. Exercise-induced fatigue can reduce blood plasma Ca~(2+) concentration, enhance in-cell Ca~(2+) concentration in myocardial cells. Rb1 can increase blood plasma Ca~(2+) concentration, decrease in-cell Ca~(2+) concentration, delay cell calcium overload. Rb1 can decrease the myocardium mechanics of exercise-induced fatigue rats and play a positive role on cardiac protective, it shows fewer negative affection compare with Varapamil.
通过连续15天,每天3小时的游泳耐力运动建立大鼠运动性疲劳模型,大鼠疲劳时游泳水淹过鼻,且经常下沉。应用自动生化分析仪器测定血浆乳酸脱氢酶,肌酸磷酸激酶,葡萄糖,Ca~(2+)变化。应用Power Lab测定标Ⅱ导联心电图(ECG),在体左心室收缩压,左室舒张末期压,室内最大升降速率,心率。为了排除神经和体液因素的影响,应用Langendorff离体灌流测定左心室收缩压,左室舒张末期压,室内最大升降速率,心率。并在细胞水平上应用绝对钙离子成像技术测定了心肌细胞[Ca~(2+)]i。
运动性疲劳可使大鼠血浆CK由对照组的357.83±50.45IU/L显著上升至558.1±101.2IU/L (P<0.01),升高55.97%; Glu由对照组的7.63±1.62mmol/L显著升高至10.28±2.08mmol/L (P<0.05),升高34.67%;Ca~(2+)由对照组的2.57±0.05mmol/L显著下降至2.21±0.11mmol/L(P<0.01),降低13.9%。过量运动性疲劳可使大鼠心脏显著增大,引起心肌肥厚,肌结构重组。心脏重量由0.573±0.03g显著增重至疲劳后的1.049±0.08 (P<0.01),增重82.89%运动性疲劳可使大鼠心电R波幅值显著增大,由0.5012±0.05mv增至0.9072±0.3152mv(P<0.01),增幅81.01%。运动性疲劳可使大鼠心肌力学指标较正常大鼠显著升高。在体LVSP显著升高,由15.88±0.47kPa增至18.14±0.19kPa (P<0.01),增幅14.24%;+dp/dt显著升高(P<0.05),增加了45.32%。对离体心脏,LVSP运动性疲劳组(5.681±0.497kPa)显著高于(P<0.01)正常组(4.539±0.389kPa),高出25.17%;+dp/dt显著升高(P<0.05),增加了30.78%。对心肌细胞,运动性疲劳可导致细胞内[Ca~(2+)]i显著升高,由正常的107.77±27.04nM上升至308.58±69.48nM,升高了186.3%。
人参皂苷单体Rb1可使运动性疲劳大鼠血浆CK的升高回复至292±63.89IU/L(P<0.01) ,下降47.68% ; Rb1可使Glu进一步上升至14.85±3.73mmol/L(P<0.05),上升44.46%; Rb1可使运动性疲劳引起的Ca~(2+)下降回升至2.47±0.08mmol/L (P<0.01),回升11.61%。运动性疲劳使大鼠血浆中Ca~(2+)浓度降低,肌细胞内Ca~(2+)增加,Rb1能有效提高血浆中Ca~(2+)浓度,而起到阻滞Ca~(2+)向细胞内流,减缓细胞钙超载的作用。Rb1对运动性疲劳引起的R波幅值降低不明显。人参皂苷单体Rb1可降低运动性疲劳大鼠心肌收缩力,对心肌起到保护作用。Rb1可使运动疲劳引起的LVSP上升回复至16.41±0.43kPa,下降9.53%; Rb1可使+dp/dt升高显著回复(P<0.01),下降了40.34%。对离体心脏,Rb1可极显著的降低运动性疲劳大鼠LVSP(2.737±0.595kPa),降低51.83%;Rb1极显著(P<0.01)的降低了+dp/dt,下降了46.53%。Rb1对正常组心肌也具有负性肌力效应,作用效果不如疲劳组明显。应用Ca~(2+)通道阻滞剂维拉帕米(Varapamil)做阳性对照,对疲劳组心肌也具有与Rb1相似的效果,作用更为明显,但可使心率显著降低。
运动性致疲劳可使大鼠心肌收缩力增强,心脏体积增大,心肌肥厚使得心功能增强,使大鼠血浆中Ca~(2+)浓度降低,心肌细胞内[Ca~(2+)]i升高。Rb1能有效提高血浆中Ca~(2+)浓度,而起到阻滞Ca~(2+)向细胞内流,减缓细胞钙超载的作用,Rb1可降低运动性疲劳大鼠心肌的收缩力,对心肌起到保护作用。
Exercise induced fatigue is body can’t keep its physiological process on an order level or can’t keep on certain sports strength. To study the mechanism of exercise induced fatigue and medical health care support improve the exercise ability and fatigue resume has a very important theory, practice, society benefit for improving exercise achievement and keeping fit. Take the data of [Ca~(2+)]i in myocardial cells, plasma biochemical indices, the apparent of heart, ECG and myocardium mechanics to explore the effect of exercise induced fatigue on rats’heart function. And then study the anti-exercise fatigue function of ginsengnoside Rb1, which can scavenge oxygen free radicals, improve the activity of SOD, block cell calcium channel opening.
The exercise-induced fatigue models in rats were established by 15 days chronic swimming training. Using the automatic biochemical analysis instruments to take the data of plasma biochemical indices; take the standardⅡ-lead ECG; take the data of myocardium mechanics in vivo and vitro; and using the ion imaging technique to measure [Ca~(2+)]i in mycardial cells.
Exercise-induced fatigue made the CK of rats blood plasma increased from 357.83±50.45IU/L to 558.1±101.2IU/L (P<0.01), increased 55.97%; Glu increased from 7.63±1.62mmol/L to 10.28±2.08mmol/L (P<0.05), increased 34.67%; Ca~(2+) decreased from 2.57±0.05mmol/L to 2.21±0.11mmol/L(P<0.01), decreased 13.9%. Exercise-induced fatigue made rats’heart increased obviously and myocardial hypertrophy. The weight of rats’heart increased from 0.573±0.03g to 1.049±0.08 (P<0.01), increased 82.89%. Exercise-induced fatigue made rats’ECG R wave increased rapidly from 0.5012±0.05mv to 0.9072±0.3152mv(P<0.01), increased 81.01%. Exercise-induced fatigue made rats’myocardium mechanics much higher than control. In vivo, exercise- induced fatigue, LVSP increased from 15.88±0.47kPa to 18.14±0.19kPa (P<0.01), increased 14.24%; +dp/dt increased obviously (P<0.05), increased 45.32%. In vitro, LVSP in Exercise-induced fatigue(5.681±0.497kPa) was much higher than control (4.539±0.389kPa, P<0.01), 25.17% higher; +dp/dt increased obviously (P<0.05) in exercise-induced fatigue rats, increased 30.78%. The [Ca~(2+)]i in fatigue myocardial cells (308.58±69.48nM) are much higher than control (107.77±27.04nM).
Ginsengnoside Rb1 can make the CK rise of exercise-induced fatigue rats blood plasma decrease to 292±63.89IU/L(P<0.01), decreased 47.68%; Rb1 can make Glu increased more to 14.85±3.73mmol/L(P<0.05), increased 44.46%; Rb1 can make it recover to 2.47±0.08mmol/L (P<0.01), increased 11.61%. Exercise-induced fatigue can reduce blood plasma Ca~(2+) concentration, enhance in-cell Ca~(2+) concentration, and Rb1 can increase blood plasma Ca~(2+) concentration, decrease in-cell Ca~(2+) concentration, delay cell calcium overload. Rb1 did little to decrease R wave in exercise-induced fatigue rats. Ginsengnoside Rb1 decreased myocardium mechanicals in fatigue rats, and protect cardiac muscle. In vivo, exercise- induced fatigue, Rb1 recovered LVSP to 16.41±0.43kPa(P<0.01), decreased 9.53%; Rb1 also recovered +dp/dt(P<0.01), decreased 40.34%. In vitro, Rb1 can reduce LVSP rapidly to 2.737±0.595kPa (P<0.01), reduced 51.83%; Rb1 decreased +dp/dt rapidly too(P<0.01), decreased 46.53%. Rb1 also has the negative myocardium mechanics in control, but not significant to fatigue. Varapamil has similar effect on fatigue hearts, and more effective, but it reduced heart rate notably.
Exercise-induced fatigue rats have higher myocardium mechanics, bigger heart, and get myocardial hypertrophy. Exercise-induced fatigue can reduce blood plasma Ca~(2+) concentration, enhance in-cell Ca~(2+) concentration in myocardial cells. Rb1 can increase blood plasma Ca~(2+) concentration, decrease in-cell Ca~(2+) concentration, delay cell calcium overload. Rb1 can decrease the myocardium mechanics of exercise-induced fatigue rats and play a positive role on cardiac protective, it shows fewer negative affection compare with Varapamil.
引文
1. 杨锡让. 实用运动生理学[M]. 北京体育大学出版社,1994.
2. Saoirse E. O’Sullivan, Christopher Bell. Training reduces autonomic cardiovascular responses to bothexercise-dependent and -independent stimuli in humans[J]. Autonomic Neuroscience: Basic and Clinical, 2001; 91: 76-84.
3. Tikuisis P , Keefe AA , & Inoue A. The effect of exercise-induced fatigue on response to cold exposure : A case study[J]. Medicine and Science in Sports and Exercise, 1999; 31(5) Supplement abstract : 891.
4. Kyoko Ohashi, Yoshiharu Yamamoto, Benjamin H. Natelson. Activity rhythm degrades after strenuous exercise inchronic fatigue syndrome[J]. Physiology & Behavior, 2002; 77: 39-44.
5. Jean Guillaume Steinberg, Marion Faucher, Chantal Guillot, Nathalie Kipson, Monique Badier, Yves Jammes. Depressed fatigue-induced oxidative stress in chronic hypoxemic humans and rats[J]. Respiratory Physiology & Neurobiology, 2004; 141: 179-189.
6. 魏安奎. 大运动量训练的运动生理学分析与探讨[J]. 中国运动医学杂志,2003; 22 (4): 399-405.
7. Asmussen E. Muscle fatigue[J]. Medicine and Science in Sports, 1979; 11: 313-321.
8. 杨磊. 运动疲劳的产生机制研究综述[J]. 武汉体育学院学报, 2002; 36(5): 47-49.
9. 运动生理学(体育学通用教材)[M]. 北京: 人民体育出版社, 1990.
10. 陈梅. 关于运动性疲劳产生及诊断的研究进展[J]. 柳州师专学报, 2002; 17(2): 103-106.
11. Edwards R H T. Human muscle function and fatigue[J]. London: Pitman Medical, 1981: 1-18.
12. Coyle E F, et al. J App l Physiol 1983; 55: 230-235.
13. Hultman E, et al. Exerc Sports SciRev, 1980; 7: 121-128.
14. Hogan M C, et al. Med Sci Sports Exerc, 1995; 27(3): 371-377.
15. Roberts D, et al. Sports Med, 1989; 7(2): 125-138.
16. Stringer W. J App l Physiol, 1992; 72(3): 954-961.
17. Nian K V, et al. Eur J App l Physiol, 1988; 57: 336-347.
18. Lin Y S, et al. Med Sci Sports Exerc, 1995; 27(1): 73-78.
19. Sjogaard G. Acta Physiol Scand, 1986; 128: 129-136.
20. Zai-Qun Liu, Xu-Yang Luo, Yun-Xiu Sun, Yan-Ping Chen, Zhi-Cai Wang. Can ginsenosides protect human erythrocytes against free-radical-induced hemolysis[J]? Biochimica et Biophysica Acta, 2002; 1572: 58-66.
21. Tsai SC, Chiao YC, Lu CC, Wang PS. Stimulation of the secretion of luteinizing hormone by ginsenoside-Rb1 in male rats[J]. Chin J Physiol (The Chinese journal of physiology.), 2003; 46(1): 1-7.
22. Wang LC, Lee TF. Effect of ginseng saponins on exercise performance in non-trained rats[J]. Planta Med (Planta medica.), 1998; 64(2): 130-133.
23. 谭涛, 王宏彬, 朱宏勋, 陈家旭, 李峰, 刘晓兰, 康纯洁, 刘燕. 中药复方元气精华调节乳酸代谢的实验研究[J]. 中医药研究, 2001; 17(2):48-50.
24. 郑师陵, 叶贤坤, 王青. 不同运动训练量与骨骼肌细胞凋亡的实验研究[J]. 中国实验诊断学, 2001; 5(6): 310-312.
25. 张钧, 许毫文, 黄淑怀. 力竭运动对大鼠心肌第二信史及心肌线粒体中离子含量的影响[J]. 浙江体育科学, 1999; 21(4): 42-46.
26. 曲绵玉, 等. 实用运动医学[M]. 北京科学技术出版社. 1996.
27. Teo TS. Wang JH. Mechanism of activation of a cyclie adenosine 3’,5’monophosphate phosphodiesterase from bovine heart by calcium ions[J]. J.Biol.Chem, 1973; 248(17): 5950.
28. 赵光, 肖德生. 力竭运动对小鼠骨骼肌 6 种元素含量的影响[J]. 体育学刊, 2003; 10(6): 55-56.
29. 王长青, 刘丽萍, 郑师陵, 柴戬臣, 容任霖, 邵瑞奇, 李增明, 王建军. 运动性疲时Ca~(2+), 线粒体膜电位的改变与细胞凋亡[J]. 体育科学, 2000; 20(3): 59-62.
30. Pool - Wilson P A. Enzyme loss and calcium exchange in is chemic or hypoxic myocardium[J]. In : Calcium Antagonists and Cardiovascular Disease Ed. L. H. Opie ,New York : Raven , 1984; 97 - 104.
31. Sittertz - Bhatkar. Localizing distribution of beta – glucoronidase in individual cells[J]. Biotechniques, 1989; 7(9): 922 - 924.
32. Ravichandrom L V. Alteration in the heart lysosmal stability in isoproterenal induced myocardial infraction in rats[J]. Biochem. Int, 1990; 22(2): 387 - 396.
33. Zharov V V. Changes on the acid phosphatase activity of themyocardium and skeletal muscle as a signal of the time of death[J]. Sud. Med. Ekspert, 1986; 29(3): 11 - 14.
34. Vihko V. Salminen A. Exhaustive exerciese ,endurance training ,and acid hydrolase activity in skeletal muscle[J]. Apple Physio, 1979; 47(1): 43 - 50.
35. Somlyo AV,et al. Elemental distribution in striated muscle and effects of hypertonicity - electron probe analysis of cryosections[J]. Cell Biology. 1977; 74: 828 - 857.
36. Somlyo AV,et al. Calcium releases and ionic changes in the saroplasmic reticulum of tetanized muscle: an electron – probe study[J]. Cell Biology, 1981; 90: 577 - 594.
37. 张德添. 电镜二元生物薄标样的制备技术及计算方法[J].军事医学科学院院刊, 1991; 15(4): 304 - 306.
38. 伏育平. 运动性疲劳状态下大鼠心肌线粒体内钙,MDA及磷脂酶A-2的变化[J]. 广州体育学院学报, 2005; 25(5): 27-30.
39. Guy EA, Jordge DF. Management of Firbromyalgia: Rationale for the use of magnesium and manic acid[J]. J Nutri Med, 1992; 22(3): 49-59.
40. Sharp WW. Terracio L , Borg TK. Contractile activity modulatesactin synthesis and turn-over in cultured neonatal rat heart cell[J]. Circ Res, 1993; 73: 172.
41. Marhan E, Koretsune Y. Cell calcium, oncogenes and hypertrophy[J]. H ypertens,1990; 15: 652.
42. Mcdermott PJ, Morgan HE. Contraction modulates the capacity for protein synthesis during growth of neonatal heart cells in culture[J]. Circ Res, 1989; 64: 542.
43. 陈丁丁, 于峰, 章涛, 戴德哉. 普萘洛尔、维拉帕米和卡普托利对L-甲状腺素性心肌肥厚的消退及抑制线粒体钙泵的作用[J]. 中国药科大学学报, 1996; 27(1): 44-47.
44. 成蓓, 李世英, 涂源淑. 神经肽Y,维拉帕米对大鼠心肌细胞肥大的影响[J]. 同济医科大学学报, 1998; 27(5): 382-384.
45. 张锁龙, 陈日新. 维拉帕米对心肌细胞肥大的影响[J]. 高血压杂志, 1997; 5(1): 19-21.
46. Kaser B. Exercise Starts and ends in the brain[J]. Eur J Appl Physiol, 2003; 90: 441-445.
47. Millet GY, Millet GP, Lattier G, et al. Alteration of neuromuscular function after a prolonged road cycling race[J]. Int J Sports Med, 2003; 24(3): 190-194.
48. Green HJ. Mechanisms of Muscle Fatigue in intense exercise[J]. J Sports Sci, 1997; 15(3): 247-256.
49. Lucia A, Carvajal A, Boraita A. et al. Heart dimensions may influence the occurrence of the heart rate deflection point in highly trained cyclist[J]. Br J Sports Med, 1999; 33(6): 387-392.
50. 沙晓林. 心血管系统引起运动疲劳的假说与讨论[J]. 中国临床康复, 2006; 10(16): 144-146.
51. 季丽萍, 冯照军, 陈才法, 孙颖. 小鼠力竭运动后及恢复期心肌和腓肠肌肌球蛋白 Ca~(2+)-ATPase活性的研究[J]. 浙江体育科学, 1999; 21(4): 47-49.
52. BRADY P S. Selenium, Vitamin E and the response to swimming stress in the rat[J]. J Nutr, 1979; 109: 1103-1109.
53. DAV IES J. Free Radical and tissue damage produced by exercise[J]. Biochem Biophy Res. Comm, 1982; 107: 1198-1205.
54. 丁树哲. 运动中内源性自由基对大鼠心肌线粒体膜分子动力学的影响[J]. 生物化学和生物物理学报, 1991; 7(23): 305.
55. 苏晓灵, 程彦斌, 王嵘, 苏明远, 王建国. 维拉帕米对缺血再灌注损伤心肌保护机制的探讨[J]. 临床心血管病杂志, 2003; 19(7): 412-415.
56. 矫勇轶, 陈小文, 刘世增, 王道生. 维拉帕米对豚鼠窒息性缺氧时心肌收缩力和心率的影响[J]. 苏州医学院学报, 1997; 17(3): 417-418.
57. 刘乃丰,黄元伟,楼定安. 维拉帕米抑制细胞DNA、RNA 和蛋白质合成的作用[J]. 浙江医科大学学报, 1990; 19: 107.
58. 王达理, 南柏松. 维拉帕米对心肌细胞的毒性作用[J]. 中国临床药理学与治疗学, 2000; 5(2): 178-179.
59. 曾庆华. 内皮素对心血管的作用[M]. 东北师范大学出版社. 1998 年 10 月第一版.
60. 马越. 人参皂苷单体 Rb1 对心肌缺血的保护作用及其机制[D]. 东北师范大学论文, 2000 年.
61. 刘俊. 人参二醇组皂苷及其单体Rb1对心肌缺血及心力衰竭动物模型的作用[D]. 东北师范大学论文, 2002年.
62. 陈立波.人参总皂苷对心肌缺血再灌注损伤的保护作用实验研究[J]. 白求恩医科大学学报, 1994; 10(4): 353.
63. 王中锋等.人参二醇组皂苷对烧伤大鼠心功能的保护作用[J]. 中药药理学报, 1995; 16(4): 345-348.
64. 钟国赣等.人参二醇组皂苷 Rb1、Rb2、Rb3、Rc 和 Rd 的 Ca~(2+)通道阻制和抗自由基作用[J]. 中国药理学报, 1995; 16(3): 255~260.
65. Liu K, Abe T , Sekine S , et al . Experimental study on the scavenging effects of ginsenosides on oxygen free radicals using model of heterotopic heart transplantation in rats[J]. Ann Thorac Cardiovasc Surg, 1998; 4 (4): 188 - 191.
66. Zhong Guogan, Jiang Yan. Calcium channel blockage and anti-free-radical actions of ginsenosides[J]. Chinese Medical Journal, 1997; 110(1): 28-29.
67. 蓝荣芳, 李志刚, 刘正湘. 人参皂苷Rb1对大鼠缺血再灌注心肌细胞Bcl22, Bax, Bad, Fas 基因表达的影响[J]. 中国组织化学与细胞化学杂志, 2002; 11(6): 149-152.
68. 曾和松, 刘正湘, 刘晓春. 人参皂苷Rb1与Re抗大鼠实验性却血再灌注心肌细胞凋亡及相关基因蛋白表达[J]. 中国物理医学与康复杂志, 2003; 25(7): 402-405.
69. 周艳玲, 徐明. 人参皂苷对大鼠缺血再灌注心肌保护作用的研究[J]. 武汉科技大学学报, 2001; 24(2): 196-198.
70. 曾庆华, 战术, 张文杰, 孙晓霞, 钟国赣. 人参皂苷单体Rb1对豚鼠心肌细胞ICa~(2+)电流阻滞作用的研究[J]. 白求恩医科大学学报, 1997; 23(3): 265-267.
71. 代友平, 于世龙, 蒋树芝, 唐国华. 人参皂苷对缺血再灌注损伤后犬心肌的保护作用[J]. 同济医科大学学报, 1996; 25(3): 210-212.
72. 李敬远, 朱珊珊, 曾因明. 人参皂苷抗离体大鼠心肌缺血再灌注损伤的作用[J]. 徐州医学院学报, 2004; 24(5): 404-407.
2. Saoirse E. O’Sullivan, Christopher Bell. Training reduces autonomic cardiovascular responses to bothexercise-dependent and -independent stimuli in humans[J]. Autonomic Neuroscience: Basic and Clinical, 2001; 91: 76-84.
3. Tikuisis P , Keefe AA , & Inoue A. The effect of exercise-induced fatigue on response to cold exposure : A case study[J]. Medicine and Science in Sports and Exercise, 1999; 31(5) Supplement abstract : 891.
4. Kyoko Ohashi, Yoshiharu Yamamoto, Benjamin H. Natelson. Activity rhythm degrades after strenuous exercise inchronic fatigue syndrome[J]. Physiology & Behavior, 2002; 77: 39-44.
5. Jean Guillaume Steinberg, Marion Faucher, Chantal Guillot, Nathalie Kipson, Monique Badier, Yves Jammes. Depressed fatigue-induced oxidative stress in chronic hypoxemic humans and rats[J]. Respiratory Physiology & Neurobiology, 2004; 141: 179-189.
6. 魏安奎. 大运动量训练的运动生理学分析与探讨[J]. 中国运动医学杂志,2003; 22 (4): 399-405.
7. Asmussen E. Muscle fatigue[J]. Medicine and Science in Sports, 1979; 11: 313-321.
8. 杨磊. 运动疲劳的产生机制研究综述[J]. 武汉体育学院学报, 2002; 36(5): 47-49.
9. 运动生理学(体育学通用教材)[M]. 北京: 人民体育出版社, 1990.
10. 陈梅. 关于运动性疲劳产生及诊断的研究进展[J]. 柳州师专学报, 2002; 17(2): 103-106.
11. Edwards R H T. Human muscle function and fatigue[J]. London: Pitman Medical, 1981: 1-18.
12. Coyle E F, et al. J App l Physiol 1983; 55: 230-235.
13. Hultman E, et al. Exerc Sports SciRev, 1980; 7: 121-128.
14. Hogan M C, et al. Med Sci Sports Exerc, 1995; 27(3): 371-377.
15. Roberts D, et al. Sports Med, 1989; 7(2): 125-138.
16. Stringer W. J App l Physiol, 1992; 72(3): 954-961.
17. Nian K V, et al. Eur J App l Physiol, 1988; 57: 336-347.
18. Lin Y S, et al. Med Sci Sports Exerc, 1995; 27(1): 73-78.
19. Sjogaard G. Acta Physiol Scand, 1986; 128: 129-136.
20. Zai-Qun Liu, Xu-Yang Luo, Yun-Xiu Sun, Yan-Ping Chen, Zhi-Cai Wang. Can ginsenosides protect human erythrocytes against free-radical-induced hemolysis[J]? Biochimica et Biophysica Acta, 2002; 1572: 58-66.
21. Tsai SC, Chiao YC, Lu CC, Wang PS. Stimulation of the secretion of luteinizing hormone by ginsenoside-Rb1 in male rats[J]. Chin J Physiol (The Chinese journal of physiology.), 2003; 46(1): 1-7.
22. Wang LC, Lee TF. Effect of ginseng saponins on exercise performance in non-trained rats[J]. Planta Med (Planta medica.), 1998; 64(2): 130-133.
23. 谭涛, 王宏彬, 朱宏勋, 陈家旭, 李峰, 刘晓兰, 康纯洁, 刘燕. 中药复方元气精华调节乳酸代谢的实验研究[J]. 中医药研究, 2001; 17(2):48-50.
24. 郑师陵, 叶贤坤, 王青. 不同运动训练量与骨骼肌细胞凋亡的实验研究[J]. 中国实验诊断学, 2001; 5(6): 310-312.
25. 张钧, 许毫文, 黄淑怀. 力竭运动对大鼠心肌第二信史及心肌线粒体中离子含量的影响[J]. 浙江体育科学, 1999; 21(4): 42-46.
26. 曲绵玉, 等. 实用运动医学[M]. 北京科学技术出版社. 1996.
27. Teo TS. Wang JH. Mechanism of activation of a cyclie adenosine 3’,5’monophosphate phosphodiesterase from bovine heart by calcium ions[J]. J.Biol.Chem, 1973; 248(17): 5950.
28. 赵光, 肖德生. 力竭运动对小鼠骨骼肌 6 种元素含量的影响[J]. 体育学刊, 2003; 10(6): 55-56.
29. 王长青, 刘丽萍, 郑师陵, 柴戬臣, 容任霖, 邵瑞奇, 李增明, 王建军. 运动性疲时Ca~(2+), 线粒体膜电位的改变与细胞凋亡[J]. 体育科学, 2000; 20(3): 59-62.
30. Pool - Wilson P A. Enzyme loss and calcium exchange in is chemic or hypoxic myocardium[J]. In : Calcium Antagonists and Cardiovascular Disease Ed. L. H. Opie ,New York : Raven , 1984; 97 - 104.
31. Sittertz - Bhatkar. Localizing distribution of beta – glucoronidase in individual cells[J]. Biotechniques, 1989; 7(9): 922 - 924.
32. Ravichandrom L V. Alteration in the heart lysosmal stability in isoproterenal induced myocardial infraction in rats[J]. Biochem. Int, 1990; 22(2): 387 - 396.
33. Zharov V V. Changes on the acid phosphatase activity of themyocardium and skeletal muscle as a signal of the time of death[J]. Sud. Med. Ekspert, 1986; 29(3): 11 - 14.
34. Vihko V. Salminen A. Exhaustive exerciese ,endurance training ,and acid hydrolase activity in skeletal muscle[J]. Apple Physio, 1979; 47(1): 43 - 50.
35. Somlyo AV,et al. Elemental distribution in striated muscle and effects of hypertonicity - electron probe analysis of cryosections[J]. Cell Biology. 1977; 74: 828 - 857.
36. Somlyo AV,et al. Calcium releases and ionic changes in the saroplasmic reticulum of tetanized muscle: an electron – probe study[J]. Cell Biology, 1981; 90: 577 - 594.
37. 张德添. 电镜二元生物薄标样的制备技术及计算方法[J].军事医学科学院院刊, 1991; 15(4): 304 - 306.
38. 伏育平. 运动性疲劳状态下大鼠心肌线粒体内钙,MDA及磷脂酶A-2的变化[J]. 广州体育学院学报, 2005; 25(5): 27-30.
39. Guy EA, Jordge DF. Management of Firbromyalgia: Rationale for the use of magnesium and manic acid[J]. J Nutri Med, 1992; 22(3): 49-59.
40. Sharp WW. Terracio L , Borg TK. Contractile activity modulatesactin synthesis and turn-over in cultured neonatal rat heart cell[J]. Circ Res, 1993; 73: 172.
41. Marhan E, Koretsune Y. Cell calcium, oncogenes and hypertrophy[J]. H ypertens,1990; 15: 652.
42. Mcdermott PJ, Morgan HE. Contraction modulates the capacity for protein synthesis during growth of neonatal heart cells in culture[J]. Circ Res, 1989; 64: 542.
43. 陈丁丁, 于峰, 章涛, 戴德哉. 普萘洛尔、维拉帕米和卡普托利对L-甲状腺素性心肌肥厚的消退及抑制线粒体钙泵的作用[J]. 中国药科大学学报, 1996; 27(1): 44-47.
44. 成蓓, 李世英, 涂源淑. 神经肽Y,维拉帕米对大鼠心肌细胞肥大的影响[J]. 同济医科大学学报, 1998; 27(5): 382-384.
45. 张锁龙, 陈日新. 维拉帕米对心肌细胞肥大的影响[J]. 高血压杂志, 1997; 5(1): 19-21.
46. Kaser B. Exercise Starts and ends in the brain[J]. Eur J Appl Physiol, 2003; 90: 441-445.
47. Millet GY, Millet GP, Lattier G, et al. Alteration of neuromuscular function after a prolonged road cycling race[J]. Int J Sports Med, 2003; 24(3): 190-194.
48. Green HJ. Mechanisms of Muscle Fatigue in intense exercise[J]. J Sports Sci, 1997; 15(3): 247-256.
49. Lucia A, Carvajal A, Boraita A. et al. Heart dimensions may influence the occurrence of the heart rate deflection point in highly trained cyclist[J]. Br J Sports Med, 1999; 33(6): 387-392.
50. 沙晓林. 心血管系统引起运动疲劳的假说与讨论[J]. 中国临床康复, 2006; 10(16): 144-146.
51. 季丽萍, 冯照军, 陈才法, 孙颖. 小鼠力竭运动后及恢复期心肌和腓肠肌肌球蛋白 Ca~(2+)-ATPase活性的研究[J]. 浙江体育科学, 1999; 21(4): 47-49.
52. BRADY P S. Selenium, Vitamin E and the response to swimming stress in the rat[J]. J Nutr, 1979; 109: 1103-1109.
53. DAV IES J. Free Radical and tissue damage produced by exercise[J]. Biochem Biophy Res. Comm, 1982; 107: 1198-1205.
54. 丁树哲. 运动中内源性自由基对大鼠心肌线粒体膜分子动力学的影响[J]. 生物化学和生物物理学报, 1991; 7(23): 305.
55. 苏晓灵, 程彦斌, 王嵘, 苏明远, 王建国. 维拉帕米对缺血再灌注损伤心肌保护机制的探讨[J]. 临床心血管病杂志, 2003; 19(7): 412-415.
56. 矫勇轶, 陈小文, 刘世增, 王道生. 维拉帕米对豚鼠窒息性缺氧时心肌收缩力和心率的影响[J]. 苏州医学院学报, 1997; 17(3): 417-418.
57. 刘乃丰,黄元伟,楼定安. 维拉帕米抑制细胞DNA、RNA 和蛋白质合成的作用[J]. 浙江医科大学学报, 1990; 19: 107.
58. 王达理, 南柏松. 维拉帕米对心肌细胞的毒性作用[J]. 中国临床药理学与治疗学, 2000; 5(2): 178-179.
59. 曾庆华. 内皮素对心血管的作用[M]. 东北师范大学出版社. 1998 年 10 月第一版.
60. 马越. 人参皂苷单体 Rb1 对心肌缺血的保护作用及其机制[D]. 东北师范大学论文, 2000 年.
61. 刘俊. 人参二醇组皂苷及其单体Rb1对心肌缺血及心力衰竭动物模型的作用[D]. 东北师范大学论文, 2002年.
62. 陈立波.人参总皂苷对心肌缺血再灌注损伤的保护作用实验研究[J]. 白求恩医科大学学报, 1994; 10(4): 353.
63. 王中锋等.人参二醇组皂苷对烧伤大鼠心功能的保护作用[J]. 中药药理学报, 1995; 16(4): 345-348.
64. 钟国赣等.人参二醇组皂苷 Rb1、Rb2、Rb3、Rc 和 Rd 的 Ca~(2+)通道阻制和抗自由基作用[J]. 中国药理学报, 1995; 16(3): 255~260.
65. Liu K, Abe T , Sekine S , et al . Experimental study on the scavenging effects of ginsenosides on oxygen free radicals using model of heterotopic heart transplantation in rats[J]. Ann Thorac Cardiovasc Surg, 1998; 4 (4): 188 - 191.
66. Zhong Guogan, Jiang Yan. Calcium channel blockage and anti-free-radical actions of ginsenosides[J]. Chinese Medical Journal, 1997; 110(1): 28-29.
67. 蓝荣芳, 李志刚, 刘正湘. 人参皂苷Rb1对大鼠缺血再灌注心肌细胞Bcl22, Bax, Bad, Fas 基因表达的影响[J]. 中国组织化学与细胞化学杂志, 2002; 11(6): 149-152.
68. 曾和松, 刘正湘, 刘晓春. 人参皂苷Rb1与Re抗大鼠实验性却血再灌注心肌细胞凋亡及相关基因蛋白表达[J]. 中国物理医学与康复杂志, 2003; 25(7): 402-405.
69. 周艳玲, 徐明. 人参皂苷对大鼠缺血再灌注心肌保护作用的研究[J]. 武汉科技大学学报, 2001; 24(2): 196-198.
70. 曾庆华, 战术, 张文杰, 孙晓霞, 钟国赣. 人参皂苷单体Rb1对豚鼠心肌细胞ICa~(2+)电流阻滞作用的研究[J]. 白求恩医科大学学报, 1997; 23(3): 265-267.
71. 代友平, 于世龙, 蒋树芝, 唐国华. 人参皂苷对缺血再灌注损伤后犬心肌的保护作用[J]. 同济医科大学学报, 1996; 25(3): 210-212.
72. 李敬远, 朱珊珊, 曾因明. 人参皂苷抗离体大鼠心肌缺血再灌注损伤的作用[J]. 徐州医学院学报, 2004; 24(5): 404-407.