Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigra...Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of highfrequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1-and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus(EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca2+-ATPase(SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase(nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated intracellular resting Ca2+ concentration([Ca2+]i) in unloaded soleus muscles. High [Ca2+]i activated calpain-1 which induced a higher degradation of desmin. Desmin degradation may loose connections between adjacent myofibrils and further misaligned Z-disc during repeated tetanic contractions. Passive stretch in unloaded muscle could preserve the stability of sarcoplasmic reticulum Ca2+ release channels by means of keeping nNOS activity, and decrease the enhanced protein level and activity of calpain to control levels in unloaded soleus muscles. Therefore, passive stretch restored normal appearance of Z-disc and resisted in part atrophy of unloaded soleus muscles. The above results indicate that enhanced fatigability of high-frequency tetanic contraction is associated to the alteration in K+ channel characteristics, and elevated SERCA activity and slow to fast transition of myosin heavy chain(MHC) isoforms increases fatigability of intermittent tetanic contraction in atrophic soleus muscle. The sarcomeric damage induced by tetanic contraction can be retarded by stretch in atrophic soleus muscles.展开更多
ABSTRACT Objective： To investigate the protective effects of a Chinese herbal formula, Taikong Yangxin Prescription （太空养心方,TKYXP） against bone deterioration in a hindlimb unloaded （tail-suspension） rat model...ABSTRACT Objective： To investigate the protective effects of a Chinese herbal formula, Taikong Yangxin Prescription （太空养心方,TKYXP） against bone deterioration in a hindlimb unloaded （tail-suspension） rat model. Methods： Thirty-two male Sprague-Dawley rats were divided into 4 groups： tail-suspension group fed with 2.5 g·kg^-1·day^-1 of TKYXP extract （high dose）, tail-suspension group fed with 1.25 g·kg^-1·day^-1 （low dose）, tail-suspended group treated with water placebo （placebo control group） and non tail-suspended group. The effects of TKYXP on bone were assessed using peripheral quantitative computed tomography （pQCT）, micro- computerized tomography （micro-CT） and three-point bending biomechanical test on the femur in vivo. Results： TKYXP had a significant protective effect against bone loss induced by tail-suspension on day 28, as shown in the reduction in bone mineral density （BMD） loss, preservation of bone micro-architecture and biomechanical strength. The administration ofhigh dose TKYXP could significantly reduce the total BMD loss by 4.8% and 8.0% at the femur and tibia regions, respectively, compared with the placebo control group （P〈0.01） on day 28. Its bone protective effect on the femur was further substantiated by the increases of the trabecular BMD （by 6.6%）, bone volume fraction （by 20.9%）, trabecular number （by 9.5%） and thickness （by 11.9%） as compared with the placebo control group. Conclusion： TKYXP may protect the bone under weightless influence from gradual structural deterioration in the tail-suspension model.展开更多
基金supported by a Natural Science Foundation of China Grant(30770805)
文摘Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of highfrequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1-and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus(EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca2+-ATPase(SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase(nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated intracellular resting Ca2+ concentration([Ca2+]i) in unloaded soleus muscles. High [Ca2+]i activated calpain-1 which induced a higher degradation of desmin. Desmin degradation may loose connections between adjacent myofibrils and further misaligned Z-disc during repeated tetanic contractions. Passive stretch in unloaded muscle could preserve the stability of sarcoplasmic reticulum Ca2+ release channels by means of keeping nNOS activity, and decrease the enhanced protein level and activity of calpain to control levels in unloaded soleus muscles. Therefore, passive stretch restored normal appearance of Z-disc and resisted in part atrophy of unloaded soleus muscles. The above results indicate that enhanced fatigability of high-frequency tetanic contraction is associated to the alteration in K+ channel characteristics, and elevated SERCA activity and slow to fast transition of myosin heavy chain(MHC) isoforms increases fatigability of intermittent tetanic contraction in atrophic soleus muscle. The sarcomeric damage induced by tetanic contraction can be retarded by stretch in atrophic soleus muscles.
基金Supported by Focused Investments Scheme:One-off Support(Scheme D)-Collaboration with the China Astronaut Research and Training Centre(No.RAC/2006/182)the Chinese University of Hong Kong,Hong Kong SAR,China
文摘ABSTRACT Objective： To investigate the protective effects of a Chinese herbal formula, Taikong Yangxin Prescription （太空养心方,TKYXP） against bone deterioration in a hindlimb unloaded （tail-suspension） rat model. Methods： Thirty-two male Sprague-Dawley rats were divided into 4 groups： tail-suspension group fed with 2.5 g·kg^-1·day^-1 of TKYXP extract （high dose）, tail-suspension group fed with 1.25 g·kg^-1·day^-1 （low dose）, tail-suspended group treated with water placebo （placebo control group） and non tail-suspended group. The effects of TKYXP on bone were assessed using peripheral quantitative computed tomography （pQCT）, micro- computerized tomography （micro-CT） and three-point bending biomechanical test on the femur in vivo. Results： TKYXP had a significant protective effect against bone loss induced by tail-suspension on day 28, as shown in the reduction in bone mineral density （BMD） loss, preservation of bone micro-architecture and biomechanical strength. The administration ofhigh dose TKYXP could significantly reduce the total BMD loss by 4.8% and 8.0% at the femur and tibia regions, respectively, compared with the placebo control group （P〈0.01） on day 28. Its bone protective effect on the femur was further substantiated by the increases of the trabecular BMD （by 6.6%）, bone volume fraction （by 20.9%）, trabecular number （by 9.5%） and thickness （by 11.9%） as compared with the placebo control group. Conclusion： TKYXP may protect the bone under weightless influence from gradual structural deterioration in the tail-suspension model.
