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
mouth occlusion pressure (P<sub>0.1</sub>) rather than inspiratory ventilation （V<sub>1</sub>）and mean inspiratory airflow （（?）） was used for expounding the mechanism of indi-vidual hypox...mouth occlusion pressure (P<sub>0.1</sub>) rather than inspiratory ventilation （V<sub>1</sub>）and mean inspiratory airflow （（?）） was used for expounding the mechanism of indi-vidual hypoxic sensitivity.Eighteen young healthy male subjects participated inthe experiment of progressive isocapnic hypoxia produced by rebreathing method.The results showed that there were significantly linear relationship （P【0.01） be-tween V<sub>1</sub> and P<sub>0.1</sub>,as well as （?） and P<sub>0.1</sub> during the hypoxic loading of twoend-tidal carbon dioxide pressure (P<sub>ETCO<sub>2</sub></sub> levels,4.3 and 5.9kPa.Ventilation in-creased with progressive hypoxia.Therefore,they all represent the useful indexesof inspiratory drive.P<sub>0.1</sub> is more sensitive than V<sub>1</sub> and （?） because it isindependent of pulmonary mechanics.展开更多
Objective: To introduce a method to calculate cardiovascular age, a new, accurate and much simpler index for assessing cardiovascular autonomic regulatory function, based on statistical analysis of heart rate and bloo...Objective: To introduce a method to calculate cardiovascular age, a new, accurate and much simpler index for assessing cardiovascular autonomic regulatory function, based on statistical analysis of heart rate and blood pressure variability (HRV and BPV) and baroreflex sensitivity (BRS) data. Methods: Firstly, HRV and BPV of 89 healthy aviation personnel were analyzed by the conventional autoregressive (AR) spectral analysis and their spontaneous BRS was obtained by the sequence method. Secondly, principal component analysis was conducted over original and derived indices of HRV, BPV and BRS data and the relevant principal components, PCi orig and PCi deri (i=1, 2, 3,...) were obtained. Finally, the equation for calculating cardiovascular age was obtained by multiple regression with the chronological age being assigned as the dependent variable and the principal components significantly related to age as the regressors. Results: The first four principal components of original indices accounted for over 90% of total variance of the indices, so did the first three principal components of derived indices. So, these seven principal components could reflect the information of cardiovascular autonomic regulation which was embodied in the 17 indices of HRV, BPV and BRS exactly with a minimal loss of information. Of the seven principal components, PC2 orig , PC4 orig and PC2 deri were negatively correlated with the chronological age ( P <0 05), whereas the PC3 orig was positively correlated with the chronological age ( P <0 01). The cardiovascular age thus calculated from the regression equation was significantly correlated with the chronological age among the 89 aviation personnel ( r =0.73, P <0 01). Conclusion: The cardiovascular age calculated based on a multi variate analysis of HRV, BPV and BRS could be regarded as a comprehensive indicator reflecting the age dependency of autonomic regulation of cardiovascular system in healthy aviation personnel.展开更多
Objective Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts.Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process.To elucidate t...Objective Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts.Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process.To elucidate the mechanism for this condition,we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted(HU)rat cerebral arteries.Methods Three-week HU was used to simulate microgravity in rats.The contractile responses to vasoconstrictors,mitochondrial fission/fusion,Ca^(2+) distribution,inositol 1,4,5-trisphosphate receptor(IP3 R)abundance,and the activities of voltage-gated K+channels(KV)and Ca^(2+)-activated K+channels(BKCa)were examined in rat cerebral vascular smooth muscle cells(VSMCs).Results An increase of cytoplasmic Ca^(2+) and a decrease of mitochondrial/sarcoplasmic reticulum(SR)Ca^(2+) were observed in HU rat cerebral VSMCs.The abundance of fusion proteins(mitofusin 1/2[MFN1/2])and fission proteins(dynamin-related protein 1[DRP1]and fission-mitochondrial 1[FIS1])was significantly downregulated and upregulated,respectively in HU rat cerebral VSMCs.The cerebrovascular contractile responses to vasoconstrictors were enhanced in HU rats compared to control rats,and IP3 R protein/mRNA levels were significantly upregulated.The current densities and open probabilities of KV and BKCa decreased and increased,respectively.Treatment with the mitochondrial-targeted antioxidant mitoTEMPO attenuated mitochondrial fission by upregulating MFN1/2 and downregulating DRP1/FIS1.It also decreased IP3 R expression levels and restored the activities of the KV and BKCa channels.MitoTEMPO restored the Ca^(2+) distribution in VSMCs and attenuated the enhanced vasoconstriction in HU rat cerebral arteries.Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.展开更多
In mechanically ventilated anesthetized dogs (pentobarbital sodium,30mg/kg) with acute lung injury induced by intravenous infusion of oleic acid(OA),changes in airflow,lung volume,and tracheal (Pao),transpulmonary (Pt...In mechanically ventilated anesthetized dogs (pentobarbital sodium,30mg/kg) with acute lung injury induced by intravenous infusion of oleic acid(OA),changes in airflow,lung volume,and tracheal (Pao),transpulmonary (Ptp)and esophageal (Pes) pressures were measured.Changes in lung mechanics werestudied before and after OA infusion at intervals,during an observation periodlasting 4h,using curve-fitting method,interrupter technique and pressure-volume(PV) loops measurement.The main findings are listed as follows:(1)Complianceand functional residual capacity (FRC) showed a marked decrease,while Pao andPtp showed a marked increase within 2h after OA.(2) Airflow resistance atexpiratory phase estimated by the curve-fitting method showed a marked increaseafter OA.(3)PV loops of the lungs or total respiratory system showed similarchanges 4h after OA,characterized by the presence of an inflexion point at theinflation limb,increased hysteresis and rightward and downward shift of the loop.It is suggested that use of the curve-fitting method in combination with the PVloop for the total respiratory system would be more appropriate for monitoringlung mechanics during mechanical ventilatory support of ARDS patients.展开更多
Background Olfactory ensheathing cells （OECs） can promote many kinds of neuron growth and axonal extension. The aim of the study was to investigate the effects of co-culturing with OECs on neuron apoptosis in vitro....Background Olfactory ensheathing cells （OECs） can promote many kinds of neuron growth and axonal extension. The aim of the study was to investigate the effects of co-culturing with OECs on neuron apoptosis in vitro. Methods Apoptosis was induced by treatment of cultured dorsal root ganglion neurons with 1 mmol/L hydrogen peroxide （H2O2）. Cells were randomly arranged into the following treatment groups. In group 1, OECs at different density （10^4/ml to 8×10^5/ml） were added immediately after H2O2 treatment and cells were co-cultured for 24 hours. In group 2, OECs were added at different time points （0, 4, 8, 12 and 24 hours） after H2O2 treatment. Apoptotic cell death was determined by Hoechst 33258 staining and flow cytometry （FCM）. Cell viability was determined by using methyl thiazoleterazolium （MTT） assays. Results The results showed in the Hoechest 33258 staining, FCM and MTT that OECs have both the density-dependent protection and time-dependent protection on neuron apoptosis. The apoptosis decreased and the dorsal root ganglion neuron viability increased, when the density of OECs was increased in co-culture groups. But further increasing OEC density above 2×10^5/ml （i.e. 8×10^5/ml） failed to exert additional protection. As the interval between adding H2O2 and adding OECs was increased, the amounts of apoptosis cells were also increased. When OECs were added 24 hours after H2O2, no significant protection was observed. Conclusion These results indicated that OECs could protect dorsal root ganglion neurons from apoptosis induced by H2O2 in a density- and time-dependent manner.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.
文摘mouth occlusion pressure (P<sub>0.1</sub>) rather than inspiratory ventilation （V<sub>1</sub>）and mean inspiratory airflow （（?）） was used for expounding the mechanism of indi-vidual hypoxic sensitivity.Eighteen young healthy male subjects participated inthe experiment of progressive isocapnic hypoxia produced by rebreathing method.The results showed that there were significantly linear relationship （P【0.01） be-tween V<sub>1</sub> and P<sub>0.1</sub>,as well as （?） and P<sub>0.1</sub> during the hypoxic loading of twoend-tidal carbon dioxide pressure (P<sub>ETCO<sub>2</sub></sub> levels,4.3 and 5.9kPa.Ventilation in-creased with progressive hypoxia.Therefore,they all represent the useful indexesof inspiratory drive.P<sub>0.1</sub> is more sensitive than V<sub>1</sub> and （?） because it isindependent of pulmonary mechanics.
文摘Objective: To introduce a method to calculate cardiovascular age, a new, accurate and much simpler index for assessing cardiovascular autonomic regulatory function, based on statistical analysis of heart rate and blood pressure variability (HRV and BPV) and baroreflex sensitivity (BRS) data. Methods: Firstly, HRV and BPV of 89 healthy aviation personnel were analyzed by the conventional autoregressive (AR) spectral analysis and their spontaneous BRS was obtained by the sequence method. Secondly, principal component analysis was conducted over original and derived indices of HRV, BPV and BRS data and the relevant principal components, PCi orig and PCi deri (i=1, 2, 3,...) were obtained. Finally, the equation for calculating cardiovascular age was obtained by multiple regression with the chronological age being assigned as the dependent variable and the principal components significantly related to age as the regressors. Results: The first four principal components of original indices accounted for over 90% of total variance of the indices, so did the first three principal components of derived indices. So, these seven principal components could reflect the information of cardiovascular autonomic regulation which was embodied in the 17 indices of HRV, BPV and BRS exactly with a minimal loss of information. Of the seven principal components, PC2 orig , PC4 orig and PC2 deri were negatively correlated with the chronological age ( P <0 05), whereas the PC3 orig was positively correlated with the chronological age ( P <0 01). The cardiovascular age thus calculated from the regression equation was significantly correlated with the chronological age among the 89 aviation personnel ( r =0.73, P <0 01). Conclusion: The cardiovascular age calculated based on a multi variate analysis of HRV, BPV and BRS could be regarded as a comprehensive indicator reflecting the age dependency of autonomic regulation of cardiovascular system in healthy aviation personnel.
基金supported by the National Natural Science Foundation of China[81871516,81571841]Youth Special Project of Chinese PLA General Hospital[QNC19052]。
文摘Objective Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts.Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process.To elucidate the mechanism for this condition,we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted(HU)rat cerebral arteries.Methods Three-week HU was used to simulate microgravity in rats.The contractile responses to vasoconstrictors,mitochondrial fission/fusion,Ca^(2+) distribution,inositol 1,4,5-trisphosphate receptor(IP3 R)abundance,and the activities of voltage-gated K+channels(KV)and Ca^(2+)-activated K+channels(BKCa)were examined in rat cerebral vascular smooth muscle cells(VSMCs).Results An increase of cytoplasmic Ca^(2+) and a decrease of mitochondrial/sarcoplasmic reticulum(SR)Ca^(2+) were observed in HU rat cerebral VSMCs.The abundance of fusion proteins(mitofusin 1/2[MFN1/2])and fission proteins(dynamin-related protein 1[DRP1]and fission-mitochondrial 1[FIS1])was significantly downregulated and upregulated,respectively in HU rat cerebral VSMCs.The cerebrovascular contractile responses to vasoconstrictors were enhanced in HU rats compared to control rats,and IP3 R protein/mRNA levels were significantly upregulated.The current densities and open probabilities of KV and BKCa decreased and increased,respectively.Treatment with the mitochondrial-targeted antioxidant mitoTEMPO attenuated mitochondrial fission by upregulating MFN1/2 and downregulating DRP1/FIS1.It also decreased IP3 R expression levels and restored the activities of the KV and BKCa channels.MitoTEMPO restored the Ca^(2+) distribution in VSMCs and attenuated the enhanced vasoconstriction in HU rat cerebral arteries.Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.
文摘In mechanically ventilated anesthetized dogs (pentobarbital sodium,30mg/kg) with acute lung injury induced by intravenous infusion of oleic acid(OA),changes in airflow,lung volume,and tracheal (Pao),transpulmonary (Ptp)and esophageal (Pes) pressures were measured.Changes in lung mechanics werestudied before and after OA infusion at intervals,during an observation periodlasting 4h,using curve-fitting method,interrupter technique and pressure-volume(PV) loops measurement.The main findings are listed as follows:(1)Complianceand functional residual capacity (FRC) showed a marked decrease,while Pao andPtp showed a marked increase within 2h after OA.(2) Airflow resistance atexpiratory phase estimated by the curve-fitting method showed a marked increaseafter OA.(3)PV loops of the lungs or total respiratory system showed similarchanges 4h after OA,characterized by the presence of an inflexion point at theinflation limb,increased hysteresis and rightward and downward shift of the loop.It is suggested that use of the curve-fitting method in combination with the PVloop for the total respiratory system would be more appropriate for monitoringlung mechanics during mechanical ventilatory support of ARDS patients.
基金This work was supported by a grant from the National NaturalScience Foundation of China(No.30070761)
文摘Background Olfactory ensheathing cells （OECs） can promote many kinds of neuron growth and axonal extension. The aim of the study was to investigate the effects of co-culturing with OECs on neuron apoptosis in vitro. Methods Apoptosis was induced by treatment of cultured dorsal root ganglion neurons with 1 mmol/L hydrogen peroxide （H2O2）. Cells were randomly arranged into the following treatment groups. In group 1, OECs at different density （10^4/ml to 8×10^5/ml） were added immediately after H2O2 treatment and cells were co-cultured for 24 hours. In group 2, OECs were added at different time points （0, 4, 8, 12 and 24 hours） after H2O2 treatment. Apoptotic cell death was determined by Hoechst 33258 staining and flow cytometry （FCM）. Cell viability was determined by using methyl thiazoleterazolium （MTT） assays. Results The results showed in the Hoechest 33258 staining, FCM and MTT that OECs have both the density-dependent protection and time-dependent protection on neuron apoptosis. The apoptosis decreased and the dorsal root ganglion neuron viability increased, when the density of OECs was increased in co-culture groups. But further increasing OEC density above 2×10^5/ml （i.e. 8×10^5/ml） failed to exert additional protection. As the interval between adding H2O2 and adding OECs was increased, the amounts of apoptosis cells were also increased. When OECs were added 24 hours after H2O2, no significant protection was observed. Conclusion These results indicated that OECs could protect dorsal root ganglion neurons from apoptosis induced by H2O2 in a density- and time-dependent manner.
