A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to ...A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.展开更多
To date, the medium and long-term space flight is urgent in need and has become a major task of our manned space flight program. There is no doubt that medium and long-term space flight has serious damaging impact upo...To date, the medium and long-term space flight is urgent in need and has become a major task of our manned space flight program. There is no doubt that medium and long-term space flight has serious damaging impact upon human physiological systems. For instance, atrophy of the lower limb anti-gravity muscle can be induced during the space flight. Muscle atrophy significantly affects the flight of astronauts in space. Most importantly, it influences the precise manipulation of the astronauts and their response capacity to emergencies on returning to the atmosphere from space. Muscle atrophy caused by weightlessness may also seriously disrupt the normal life and ＇work of the astronauts during the re-adaptation period. Here we summarize the corresponding research concentrating on weightlessness-induced changes of muscular structure and function. By combining research on muscle pain, which is a common clinical pain disease, we further provide a hypothesis concerning a dynamic feedback model of ＂weightlessness condition → muscular atrophy ←→ muscle pain＂. This may be useful to explore the neural mechanisms underlying the occurrence and development of muscular atrophy and muscle pain, through the key study of muscle spindle, and furthermore provide more effective therapy for clinical treatment.展开更多
AIM： To evaluate the effect of long weightlessness on retina and optic nerve in suspension （TS） rats. -term tail METHODS： A stimulated weightlessness model was established by suspending rats tail. After 12wk, the...AIM： To evaluate the effect of long weightlessness on retina and optic nerve in suspension （TS） rats. -term tail METHODS： A stimulated weightlessness model was established by suspending rats tail. After 12wk, the ultrastructure and the number of optic nerve axons were observed by transmission electron microscope. The number of survival retinal ganglion cells （RGCs） was calculated by fluorescent gold retrograde labeling. Retina cells apoptosis was detected by TUNEL staining. The function of optic nerve and retina was evaluated by the visual evoked potential （VEP） and oscillatory potentials （Ops）. RESULTS： The optic nerve axons were swollen and sparsely aligned, and the lamellar separation and myelin disintegration occurred after 12wk in TS rats. The density of optic nerve axons was 32.23±3.92 （ ys 37.43±4.13, P= 0.0145）, the RGCs density was 1645 ±46 cells/mm^2 （vs 1867±54 cells/mm^2 F=0.0000）, the incidence rate of retinal cells apoptosis was 5.38%±0.53% （ vs 4.75%±0.54%, P= 0.0238）, the amplitude of VEP-P100 was 15.43±2.14 μV （vs 17.67±2.17 μV, P=0.0424）, the latency of VEP-P100 was 69.05v5.34ms （vs 62.43±4.87ms P=0.0143） and the sum amplitude of Ops was 81.05±8.34 μV （Ys 91.67± 10.21 μV, P=0.0280） in TS group and the control group, respectively. CONCLUSION： Long-term weightlessness can induce the ultrastructural changes and functional depress of the optic nerve, as well as retinal cell damages in TS rats.展开更多
Objective:To prohe into the influences of Chinese herbal compound on the growth and metabolism of weight-bearing bones of tail-suspended rats.Methods:Twenty-four male St) rats were randomly divided into blank conlrol ...Objective:To prohe into the influences of Chinese herbal compound on the growth and metabolism of weight-bearing bones of tail-suspended rats.Methods:Twenty-four male St) rats were randomly divided into blank conlrol group leighti.tail-suspended conlrol group(eight) and Chinese medicine treatment group leighti according to their weights.No treatment was done for the blank conlrol group.Double distilled water lavage was performed daily for the tail-suspended control group.On the basis of the tail-suspended rat model,the rats were given Chinese herbal compound lavage every day in Chinese medicine treatment group.This compound includes mulberry,Poria cocas and barbary wolfberry.etc.The lest cycle was four weeks.The rats were killed after the experiment.The right femoral bone was taken out for the physical measurements, and the left femoral bone was for the three-point beading test.The influences of Chinese herbal compound on femoral hone growth and biomechanicsl properties of simulated weightlessness rats were observed.Results:(1) After simulated weightlessness(tail-suspension),compared with the blank control group,all the physiological indexes of rat femoral bone decreased in tailsuspended group and Chinese medicine treatment group(P【0.05).The strength and rigidity of rat femoral bone decreased in tail-suspended group(P【0.01).the maximum load and rigidity coefficient also decreased with the inereasing toughness coefficient in the control group(P【0.01). i2i After the countermeasure of Chinese herbal compound,each biomcchanical indexes showed the tendency of increasing in Chinese medicine treatment group,and theses indexes were close to those of the blank control group(P【0.05),which indicated that(he bone loss caused by simulated weightlessness was improved.Conclusions:Chinese herbal compound for tonifying kidney could effectively prevent the bone loss and have some enhancements on the bone hiomechanical properties.展开更多
This study investigated the tight junction（TJ） protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness.Twenty-four Wistar rats were randomly divided into three group...This study investigated the tight junction（TJ） protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness.Twenty-four Wistar rats were randomly divided into three groups：CON group（n=8）,control; SUS-14 d group（n=8）,tail-suspension for 14 days; SUS-21 d group（n=8）,tail-suspension for 21 days.Occludin and Zonula Occluden-1（ZO-1） expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR.Plasma levels of diamine oxidase（DAO） and d-lactate were determined using enzymatic spectrophotometry.Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups.The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group,and significantly lower than those in CON group（Occldin：0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1：0.82±0.01 vs 1.00±0.02 vs 1.55±0.01,P〈0.01）.Moreover,the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group,and significantly higher than those in CON group（DAO：27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate：37.86±0.74 vs 28.26±1.01 vs 17.76±0.91,P〈0.01）.There were significant negative correlations between occludin or ZO-1 expression levels and DAO（r2=0.9014,r2=0.9355,P〈0.01） or d-lactate levels（r2=0.8989,r2=0.9331,P〈0.01）.Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model.The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.展开更多
Objective: To observe the effect of simulated weightlessness on stress-strain relationship and the structural change of rabbit femoral vein. Methods: After seting up the Head-Down Tilt (-20°) (HDT) model to simul...Objective: To observe the effect of simulated weightlessness on stress-strain relationship and the structural change of rabbit femoral vein. Methods: After seting up the Head-Down Tilt (-20°) (HDT) model to simulate weightlessness, 24 healthy male New-Zealand Rabbits were randomly divided into HDT-21d group, HDT-10d group and control group, with 8 in each. Femoral venous strips and rings were used to make uniaxial tensile test of the longitudinal and circumferential specimens of the vessels. At last we observed the microstructure of femoral vein wall in 3 groups. Results : With the increasing of load stress, both longitudinal and circumferential strains of vein samples from 3 groups increased significantly (P<0. 01). With the decrease of unload stress, strains decrease obviously (P<0. 01). The unloaded longitudinal and the circumferential strain from 3 groups increased much than those of the loaded. Under the same stress (longitudinal 0-2. 0 g, circumferential 0. 5-1. 0 g) , HDT-21d group and HDT-10d group increased obviously in tlie longitudinal or circumferential strain (load and unload) than control, and HDT-21d increased much than that of HDT-10d. The contents and structures of femoral vein walls of HDT-rabbits changed significantly. Some endotheli-um cells of femoral vein became short, columnar or cubic even fell off. Smooth muscle layers became thinner. Conclusion:The compliance of femoral venous increased significantly after weightlessness-simulation and increased much obviously after 21d-HDT than that of 10 d. The structure of femoral vein wall changed obviously. The changes may be one reason for the increase of femoral vein compliance.展开更多
Objective To study the effects of simulated weightlessness induced by tail-suspension on reproduction in adult male rats and its mechanisms. Methods Twenty Spraque-Dawley adult male rats were randomly divided into two...Objective To study the effects of simulated weightlessness induced by tail-suspension on reproduction in adult male rats and its mechanisms. Methods Twenty Spraque-Dawley adult male rats were randomly divided into two groups: the experimental group and control group. Rats in the experimental group were tail-suspended for 14 days. After the treatment, the weight and morphology of testis, the quantity and quality of sperm, the level of serum testosterone and the apoptosis rate of testicular cells were observed. Results Compared with the control, the testicular weight, the quantity and quality of sperm, the level of serum testosterone significantly decreased (P<0.05) while the apoptosis rate of testicular cells significantly increased (P<0.05) in tail-suspended rats. In addition, hematoxylin and eosin (HE) staining showed that seminiferous tubules atrophied, spermatogenic cells decreased, seminiferous epithelial cells disintegrated and shed, and the lumina were azoospermic. Conclusion Simulated weightlessness induced by tail-suspension has a harmful effect on male reproduction of adult rats by increasing the apoptosis of testicular cells.展开更多
Objective To study the morphological changes of soleus muscle spindle and electrical activity of neurons in Red Nucleus(RN) of the rat after 2 weeks' simulated weightlessness, and to reveal the interaction between...Objective To study the morphological changes of soleus muscle spindle and electrical activity of neurons in Red Nucleus(RN) of the rat after 2 weeks' simulated weightlessness, and to reveal the interaction between proprioceptive inputs of muscle spindles and reciprocal alterations in RN under simulated weightlessness. Methods Twenty female rats were exposed to weightlessness simulated by tail-suspension for 14 days (SW-14d). Body weight(200-220g) matched female rats were control group(Con). The morphological changes in isolated muscle spindle of soleus muscle, the discharges of red nucleus neurons were observed after 14d tail-suspensions by silver staining and extracellular recording respectively. Results Compared with control group ,the nerve ending of muscle spindle in SW-14d was distorted, degenerated and dissolved; the diameters of intrafusal fibers and capsule in equatorial region of soleus muscle spindles were diminished(P<0.05). The spontaneous cell activity and discharge of RN neurons (spikes/s) induced by afferent firing from muscle spindles after injection of succinylcholine were reduced after 2 weeks' simulated weightlessness respectively (18.44±5.96 vs. 10.19±6.88, 32.50±8.08 vs. 16.86±5.97, P<0.01). Conclusion The degeneration of muscle spindle induced by simulated weightlessness may be one of the causes that led to alterations in discharges of RN.展开更多
Objective: To observe Fos expression after transient decrease of blood pressure in catecholaminergic neurons of the medullary visceral zone(MVZ) in simulated weightlessness rats. Methods: Simulated weightlessness was ...Objective: To observe Fos expression after transient decrease of blood pressure in catecholaminergic neurons of the medullary visceral zone(MVZ) in simulated weightlessness rats. Methods: Simulated weightlessness was abtained by tail suspension for 4 weeks, and transient decrease of blood pressure was induced by intravenous injection of sodium nitroprusside. Fos expression in catechlaminergic neurons of MVZ were visualized by an immunohistochemical double-labeling technique with anti-Fos and anti-tyrosine hydroxylase (TH) antibodies. Results: The decrease of blood pressure in the simulated weightlessness rats resulted in Fos expression in many neurons of the medulla oblongata, and they were primarily localized in the MVZ. In the MVZ, Fos-positive neurons were concentrated in the nucleus of the solitary tract (NTS) and ventrolateral region of the medulla (VLM). On the other hand, the numbers of Fos-positive neurons in MVZ were smaller than that of control rats (treated with tail suspension or intravenous injection of sodium nitroprusside only). Although some TH-positive neurons were found to be Fos-positive, the proportion of TH/Fos double-labeled neurons was much lower than that of the control rats; intensity of TH-like immunoreactivity was also reduced. Conclusion: The decrease of Fos-positive neurons and proportion of catechlaminergic neurons expressing Fos protein may result from decrease of parasympathetic activity in the simulated weightlessness rats.展开更多
BACKGROUND： Expression of Fos in neurons of periaqueductal gray （PAG） is used to reflect the excitability. However, changes of expression of Fos in neurons of PAG are caused by injured electrostimulation after simu...BACKGROUND： Expression of Fos in neurons of periaqueductal gray （PAG） is used to reflect the excitability. However, changes of expression of Fos in neurons of PAG are caused by injured electrostimulation after simulated weightlessness, and the relationship between pretreatment and injection of succinylcholine has not been determined yet. OBJECTIVE ： To investigate the changes of expression of Fos in PAG induced by injured electrostimulation pretreatment and injection of succinylcholine at 2 weeks after simulated weightlessness.DESIGN： Observational and controlled animal study.SETTING： Department of Physiology, Medical School, Xi＇an Jiaotong University; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education. MATERIALS： A total of 24 adult female SD rats, of clean grade and weighing 180-220 g, were selected in this study. METHODS： The experiment was completed in the Experimental Animal Center of Xi＇an Jiaotong University.① All rats were randomly divided into 2 groups according to body mass： simulated weightlessness group and control group with 12 in each group. And then, each group was also divided into 3 subgroups： electrostimulation group, succinylcholine-pretreatment group and succinylcholine-injection group with 4 in each subgroup. ②The model of weightlessness was simulated by tail-suspended female rats, which were described and modified by Cheng Jie. Rats in normal control group were given the same interventions as simulated weightlessness group except for tail-suspended. ③ Experimental method： The rats in electrostimulation group were given nociceptive stimulus by a pair of subcutaneous electrodes inserted into 1 and 5 claw of left hindlimb. The stimulus （current： 10 mA; duration： 1 ms; interval： 1 s） lasted for 30 minutes. The rats in succinylcholine-pretreatment group received stimulus after intravenous administration of succinylcholine, rats in succinylcholine-injection group were not given stimulus, just received succinylcholine. ④ All rats were perfused and fixed after 2 hours from the end of stimulation. The brains were removed, and serial frozen sections of midbrain were stained using immunocytochemical method, observed and taken photos under light-microscope. The number and morphological characters of Fos-immunoreactive （Fos-IR） neurons in ventrolateral part of PAG were investigated. MAIN OUTCOME MEASURES： The alterations in number and morphological characters of Fos-IR neurons in ventrolateral PAG of all rats.RESULTS： A total of 24 rats were involved in the final analysis. ① The morphological changes of Fos-IR neurons： The expressions of Fos in ventrolateral part of PAG were observed in both control and simulated weightlessness groups rats after being given nociceptive stimulus. As compared with control group, Fos-IR neurons in simulated weightlessness group were dyed lightly, cellular integrity was impaired, and cellular verge was unclear. ② The numbers of Fos-IR neurons： In control group, the numbers of Fos-IR neurons in ventrolateral part of PAG in simulated weightlessness group were obviously lower than succinylcholine-pretreatment group, but obviously higher than succinylcholine-injection group （46.94±3.38, 71.06±8.96 and 35.04±4.62, respectively, P 〈 0.05）. In 14-day simulated weightlessness group, the numbers of Fos-IR neurons in electrostimulation group were also obviously lower than succinylcholine-pretreatment group, and obviously higher than succinylcholine-injection group （27.77±3.27, 32.91±2.99 and 11.75±1.00, respectively, P 〈 0.05）. The numbers of Fos-IR neurons in all subgroups in control group were obviously higher than those subgroups in simulated weightlessness group. Compared with electrostimulation group, the percentage of expression of Fos in ventrolateral part of PAG responsed to nociceptive stimulus after administration of succinylcholine （SCH） was increased to 51.83% in control group and 18.51% in simulated weightlessness group.CONCLUSION ：① The expression of Fos in neurons in ventrolateral part of PAG were increased by the pretreatment of SCH before nociceptive stimulus.② Nociceptive stimulus could increase the expression of Fos in neurons in ventrolateral part of PAG. ③ The numbers of Fos-IR neurons in ventrolateral part of PAG were decreased obviously after 2-week simulated weightlessness.展开更多
AIM:To analyze visual dysfunction in rats under simulated weightlessness(SW)by examining trans-laminar cribrosa pressure difference(TLCPD)and neuroimmune responses.METHODS:The 72 male Sprague-Dawley rats were randomly...AIM:To analyze visual dysfunction in rats under simulated weightlessness(SW)by examining trans-laminar cribrosa pressure difference(TLCPD)and neuroimmune responses.METHODS:The 72 male Sprague-Dawley rats were randomly assigned into two groups(ground control and hindlimb unloading-simulated microgravity)using stratified randomization,with each group further subdivided into three exposure durations:SW 2-week(SW-2W),4-week(SW-4W),and 8-week(SW-8W),n=12 per subgroup.At the designated time points for each group,intraocular pressure(IOP)and intracranial pressure(ICP)were measured,and the trans-laminar cribrosa pressure difference(TLCPD)was calculated.Additionally,optomotor response(OMR),electroretinography(ERG),and optical coherence tomography(OCT)were performed.The number of retinal ganglion cells(RGCs)was quantified via immunofluorescence,the activation of astrocytes and microglial cells was determined,and Sholl analysis was conducted to assess the function and morphology of microglial cells.Data were analyzed with SPSS and GraphPad Prism(P<0.05).RESULTS:Under prolonged simulated microgravity,rats exhibited a progressive increase in both IOP and ICP,with the most pronounced rise observed at 8wk.Concurrently,the TLCPD shifted from a negative value in controls to a positive value.These pressure alterations were associated with retinal dysfunction,as evidenced by significant reductions in ERG b-wave and photopic negative response(PhNR)amplitudes.OCT and histological analyses revealed subtle photoreceptor layer damage:while the inner nuclear layer(INL)thickness remained relatively unchanged,the outer nuclear layer(ONL)thinned significantly,and the nerve fiber layer-ganglion cell layer complex thickness(NFL-GCL)complex initially thickened before later thinning.Immunofluorescence further demonstrated marked neuroimmune activation,with astrocytes transitioning from having large cell bodies with small,elongated,sparse processes to a phenotype characterized by compact,enlarged nuclei and aggregated processes,alongside notable RGC loss.CONCLUSION:Based on the results from the simulated microgravity rat model,microgravity-induced changes in dual-chamber pressure,and neuroimmune responses in the retina may play a key role in visual dysfunction.Specifically,the activation of retinal neuroimmune cells(astrocytes and microglial cells)induced by mechanical stress appears to be central to retinal and optic nerve damage.展开更多
Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive...Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive thyroid-related cell lines cultured under simulated microgravity.Methods:Five thyroid-related cell lines—normal thyrocytes(Nthy-ori 3-1),papillary thyroid cancer(PTC)cells(SNU-790,TPC-1),poorly differentiated thyroid cancer cell(BCPAP),and anaplastic thyroid cancer cell(SNU-80)—were cultured under simulated microgravity(10-3 g)using a clinostat.Differentially expressed genes(DEGs)were analyzed using cDNA microarray,followed by functional annotation and assessment of aggressiveness via Transwell migration and invasion assays.Results:DEG analysis under simulated microgravity revealed distinct gene expression profiles by gravity condition,with 2980 DEGs in SNU-790,1033 in BCPAP,562 in TPC-1,477 in Nthy-ori 3-1,and 246 in SNU-80,as confirmed by hierarchical clustering.In PTC cell lines(SNU-790,TPC-1),G2–M phase–related genes were upregulated.In non-PTC cell lines(BCPAP,SNU-80),genes associated with innate immune response,Toll-like receptor signaling,were upregulated,whereas Hypoxia-Inducible Factor 1-alpha(HIF-1α)signaling-related genes were downregulated.Additionally,under simulated microgravity,significant migration was observed in SNU-790(3×104 cells)and BCPAP(2×104 and 3×104),while significant invasion occurred in SNU-790,Nthy-ori 3-1,and BCPAP at a seeding density of 2×104.Other conditions showed no significant differences.Conclusion:This study comprehensively evaluates the effects of simulated microgravity using a diverse panel of thyroid-related cell lines.Thesefindings provide valuable insight into how microgravity could influence cancer biology,emphasizing the importance of further research on cancer behavior in space environments and its implications for human health during long-term space missions.展开更多
The Chinese space station will be built around 2020. As a national space laboratory, it will offer unique opportunities for studying the physiological effects of weightlessness and the efficacy of the countermeasures ...The Chinese space station will be built around 2020. As a national space laboratory, it will offer unique opportunities for studying the physiological effects of weightlessness and the efficacy of the countermeasures against such effects. In this paper, we described the development of countermeasure systems in the Chinese space program. To emphasize the need of the Chinese space program to implement its own program for developing countermeasures, we reviewed the literature on the negative physiological effects of weightlessness, the challenges of completing missions, the development of countermeasure devices, the establishment of countermeasure programs, and the efficacy of the countermeasure techniques in American and Russian manned spaceflights. In addition, a brief overview was provided on the Chinese research and development on countermeasures to discuss the current status and goals of the development of countermeasures against physiological problems associated with weightlessness.展开更多
基金supported by the Army Laboratory Animal Foundation of China,No.SYDW[2020]22(to TC)the Shaanxi Provincial Key R&D Plan General Project of China,No.2022SF-236(to YM)the National Natural Science Foundation of China,No.82202070(to TC)。
文摘A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.
基金supported by the National Natural Science Foundation of China (No. 30971424)
文摘To date, the medium and long-term space flight is urgent in need and has become a major task of our manned space flight program. There is no doubt that medium and long-term space flight has serious damaging impact upon human physiological systems. For instance, atrophy of the lower limb anti-gravity muscle can be induced during the space flight. Muscle atrophy significantly affects the flight of astronauts in space. Most importantly, it influences the precise manipulation of the astronauts and their response capacity to emergencies on returning to the atmosphere from space. Muscle atrophy caused by weightlessness may also seriously disrupt the normal life and ＇work of the astronauts during the re-adaptation period. Here we summarize the corresponding research concentrating on weightlessness-induced changes of muscular structure and function. By combining research on muscle pain, which is a common clinical pain disease, we further provide a hypothesis concerning a dynamic feedback model of ＂weightlessness condition → muscular atrophy ←→ muscle pain＂. This may be useful to explore the neural mechanisms underlying the occurrence and development of muscular atrophy and muscle pain, through the key study of muscle spindle, and furthermore provide more effective therapy for clinical treatment.
基金Supported by the National Natural Scientific Foundation of China (No. 81271016)
文摘AIM： To evaluate the effect of long weightlessness on retina and optic nerve in suspension （TS） rats. -term tail METHODS： A stimulated weightlessness model was established by suspending rats tail. After 12wk, the ultrastructure and the number of optic nerve axons were observed by transmission electron microscope. The number of survival retinal ganglion cells （RGCs） was calculated by fluorescent gold retrograde labeling. Retina cells apoptosis was detected by TUNEL staining. The function of optic nerve and retina was evaluated by the visual evoked potential （VEP） and oscillatory potentials （Ops）. RESULTS： The optic nerve axons were swollen and sparsely aligned, and the lamellar separation and myelin disintegration occurred after 12wk in TS rats. The density of optic nerve axons was 32.23±3.92 （ ys 37.43±4.13, P= 0.0145）, the RGCs density was 1645 ±46 cells/mm^2 （vs 1867±54 cells/mm^2 F=0.0000）, the incidence rate of retinal cells apoptosis was 5.38%±0.53% （ vs 4.75%±0.54%, P= 0.0238）, the amplitude of VEP-P100 was 15.43±2.14 μV （vs 17.67±2.17 μV, P=0.0424）, the latency of VEP-P100 was 69.05v5.34ms （vs 62.43±4.87ms P=0.0143） and the sum amplitude of Ops was 81.05±8.34 μV （Ys 91.67± 10.21 μV, P=0.0280） in TS group and the control group, respectively. CONCLUSION： Long-term weightlessness can induce the ultrastructural changes and functional depress of the optic nerve, as well as retinal cell damages in TS rats.
文摘Objective:To prohe into the influences of Chinese herbal compound on the growth and metabolism of weight-bearing bones of tail-suspended rats.Methods:Twenty-four male St) rats were randomly divided into blank conlrol group leighti.tail-suspended conlrol group(eight) and Chinese medicine treatment group leighti according to their weights.No treatment was done for the blank conlrol group.Double distilled water lavage was performed daily for the tail-suspended control group.On the basis of the tail-suspended rat model,the rats were given Chinese herbal compound lavage every day in Chinese medicine treatment group.This compound includes mulberry,Poria cocas and barbary wolfberry.etc.The lest cycle was four weeks.The rats were killed after the experiment.The right femoral bone was taken out for the physical measurements, and the left femoral bone was for the three-point beading test.The influences of Chinese herbal compound on femoral hone growth and biomechanicsl properties of simulated weightlessness rats were observed.Results:(1) After simulated weightlessness(tail-suspension),compared with the blank control group,all the physiological indexes of rat femoral bone decreased in tailsuspended group and Chinese medicine treatment group(P【0.05).The strength and rigidity of rat femoral bone decreased in tail-suspended group(P【0.01).the maximum load and rigidity coefficient also decreased with the inereasing toughness coefficient in the control group(P【0.01). i2i After the countermeasure of Chinese herbal compound,each biomcchanical indexes showed the tendency of increasing in Chinese medicine treatment group,and theses indexes were close to those of the blank control group(P【0.05),which indicated that(he bone loss caused by simulated weightlessness was improved.Conclusions:Chinese herbal compound for tonifying kidney could effectively prevent the bone loss and have some enhancements on the bone hiomechanical properties.
文摘This study investigated the tight junction（TJ） protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness.Twenty-four Wistar rats were randomly divided into three groups：CON group（n=8）,control; SUS-14 d group（n=8）,tail-suspension for 14 days; SUS-21 d group（n=8）,tail-suspension for 21 days.Occludin and Zonula Occluden-1（ZO-1） expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR.Plasma levels of diamine oxidase（DAO） and d-lactate were determined using enzymatic spectrophotometry.Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups.The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group,and significantly lower than those in CON group（Occldin：0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1：0.82±0.01 vs 1.00±0.02 vs 1.55±0.01,P〈0.01）.Moreover,the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group,and significantly higher than those in CON group（DAO：27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate：37.86±0.74 vs 28.26±1.01 vs 17.76±0.91,P〈0.01）.There were significant negative correlations between occludin or ZO-1 expression levels and DAO（r2=0.9014,r2=0.9355,P〈0.01） or d-lactate levels（r2=0.8989,r2=0.9331,P〈0.01）.Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model.The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.
基金Supported by Grant from the National Natural Science Foundation of China(30000197)
文摘Objective: To observe the effect of simulated weightlessness on stress-strain relationship and the structural change of rabbit femoral vein. Methods: After seting up the Head-Down Tilt (-20°) (HDT) model to simulate weightlessness, 24 healthy male New-Zealand Rabbits were randomly divided into HDT-21d group, HDT-10d group and control group, with 8 in each. Femoral venous strips and rings were used to make uniaxial tensile test of the longitudinal and circumferential specimens of the vessels. At last we observed the microstructure of femoral vein wall in 3 groups. Results : With the increasing of load stress, both longitudinal and circumferential strains of vein samples from 3 groups increased significantly (P<0. 01). With the decrease of unload stress, strains decrease obviously (P<0. 01). The unloaded longitudinal and the circumferential strain from 3 groups increased much than those of the loaded. Under the same stress (longitudinal 0-2. 0 g, circumferential 0. 5-1. 0 g) , HDT-21d group and HDT-10d group increased obviously in tlie longitudinal or circumferential strain (load and unload) than control, and HDT-21d increased much than that of HDT-10d. The contents and structures of femoral vein walls of HDT-rabbits changed significantly. Some endotheli-um cells of femoral vein became short, columnar or cubic even fell off. Smooth muscle layers became thinner. Conclusion:The compliance of femoral venous increased significantly after weightlessness-simulation and increased much obviously after 21d-HDT than that of 10 d. The structure of femoral vein wall changed obviously. The changes may be one reason for the increase of femoral vein compliance.
基金This work was supported by the Scientific Technology Planning Foundation of Shaanxi Province (No.2005K15-G2) ,and the Traditional Medicine Administration Bureau Foundation of Shaanxi Province (No.2005024)
文摘Objective To study the effects of simulated weightlessness induced by tail-suspension on reproduction in adult male rats and its mechanisms. Methods Twenty Spraque-Dawley adult male rats were randomly divided into two groups: the experimental group and control group. Rats in the experimental group were tail-suspended for 14 days. After the treatment, the weight and morphology of testis, the quantity and quality of sperm, the level of serum testosterone and the apoptosis rate of testicular cells were observed. Results Compared with the control, the testicular weight, the quantity and quality of sperm, the level of serum testosterone significantly decreased (P<0.05) while the apoptosis rate of testicular cells significantly increased (P<0.05) in tail-suspended rats. In addition, hematoxylin and eosin (HE) staining showed that seminiferous tubules atrophied, spermatogenic cells decreased, seminiferous epithelial cells disintegrated and shed, and the lumina were azoospermic. Conclusion Simulated weightlessness induced by tail-suspension has a harmful effect on male reproduction of adult rats by increasing the apoptosis of testicular cells.
基金This project was supported by the National Natural Science Foundation of China (No.30300106)
文摘Objective To study the morphological changes of soleus muscle spindle and electrical activity of neurons in Red Nucleus(RN) of the rat after 2 weeks' simulated weightlessness, and to reveal the interaction between proprioceptive inputs of muscle spindles and reciprocal alterations in RN under simulated weightlessness. Methods Twenty female rats were exposed to weightlessness simulated by tail-suspension for 14 days (SW-14d). Body weight(200-220g) matched female rats were control group(Con). The morphological changes in isolated muscle spindle of soleus muscle, the discharges of red nucleus neurons were observed after 14d tail-suspensions by silver staining and extracellular recording respectively. Results Compared with control group ,the nerve ending of muscle spindle in SW-14d was distorted, degenerated and dissolved; the diameters of intrafusal fibers and capsule in equatorial region of soleus muscle spindles were diminished(P<0.05). The spontaneous cell activity and discharge of RN neurons (spikes/s) induced by afferent firing from muscle spindles after injection of succinylcholine were reduced after 2 weeks' simulated weightlessness respectively (18.44±5.96 vs. 10.19±6.88, 32.50±8.08 vs. 16.86±5.97, P<0.01). Conclusion The degeneration of muscle spindle induced by simulated weightlessness may be one of the causes that led to alterations in discharges of RN.
文摘Objective: To observe Fos expression after transient decrease of blood pressure in catecholaminergic neurons of the medullary visceral zone(MVZ) in simulated weightlessness rats. Methods: Simulated weightlessness was abtained by tail suspension for 4 weeks, and transient decrease of blood pressure was induced by intravenous injection of sodium nitroprusside. Fos expression in catechlaminergic neurons of MVZ were visualized by an immunohistochemical double-labeling technique with anti-Fos and anti-tyrosine hydroxylase (TH) antibodies. Results: The decrease of blood pressure in the simulated weightlessness rats resulted in Fos expression in many neurons of the medulla oblongata, and they were primarily localized in the MVZ. In the MVZ, Fos-positive neurons were concentrated in the nucleus of the solitary tract (NTS) and ventrolateral region of the medulla (VLM). On the other hand, the numbers of Fos-positive neurons in MVZ were smaller than that of control rats (treated with tail suspension or intravenous injection of sodium nitroprusside only). Although some TH-positive neurons were found to be Fos-positive, the proportion of TH/Fos double-labeled neurons was much lower than that of the control rats; intensity of TH-like immunoreactivity was also reduced. Conclusion: The decrease of Fos-positive neurons and proportion of catechlaminergic neurons expressing Fos protein may result from decrease of parasympathetic activity in the simulated weightlessness rats.
基金the National Natural Science Foundation of China, No. 30300106
文摘BACKGROUND： Expression of Fos in neurons of periaqueductal gray （PAG） is used to reflect the excitability. However, changes of expression of Fos in neurons of PAG are caused by injured electrostimulation after simulated weightlessness, and the relationship between pretreatment and injection of succinylcholine has not been determined yet. OBJECTIVE ： To investigate the changes of expression of Fos in PAG induced by injured electrostimulation pretreatment and injection of succinylcholine at 2 weeks after simulated weightlessness.DESIGN： Observational and controlled animal study.SETTING： Department of Physiology, Medical School, Xi＇an Jiaotong University; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education. MATERIALS： A total of 24 adult female SD rats, of clean grade and weighing 180-220 g, were selected in this study. METHODS： The experiment was completed in the Experimental Animal Center of Xi＇an Jiaotong University.① All rats were randomly divided into 2 groups according to body mass： simulated weightlessness group and control group with 12 in each group. And then, each group was also divided into 3 subgroups： electrostimulation group, succinylcholine-pretreatment group and succinylcholine-injection group with 4 in each subgroup. ②The model of weightlessness was simulated by tail-suspended female rats, which were described and modified by Cheng Jie. Rats in normal control group were given the same interventions as simulated weightlessness group except for tail-suspended. ③ Experimental method： The rats in electrostimulation group were given nociceptive stimulus by a pair of subcutaneous electrodes inserted into 1 and 5 claw of left hindlimb. The stimulus （current： 10 mA; duration： 1 ms; interval： 1 s） lasted for 30 minutes. The rats in succinylcholine-pretreatment group received stimulus after intravenous administration of succinylcholine, rats in succinylcholine-injection group were not given stimulus, just received succinylcholine. ④ All rats were perfused and fixed after 2 hours from the end of stimulation. The brains were removed, and serial frozen sections of midbrain were stained using immunocytochemical method, observed and taken photos under light-microscope. The number and morphological characters of Fos-immunoreactive （Fos-IR） neurons in ventrolateral part of PAG were investigated. MAIN OUTCOME MEASURES： The alterations in number and morphological characters of Fos-IR neurons in ventrolateral PAG of all rats.RESULTS： A total of 24 rats were involved in the final analysis. ① The morphological changes of Fos-IR neurons： The expressions of Fos in ventrolateral part of PAG were observed in both control and simulated weightlessness groups rats after being given nociceptive stimulus. As compared with control group, Fos-IR neurons in simulated weightlessness group were dyed lightly, cellular integrity was impaired, and cellular verge was unclear. ② The numbers of Fos-IR neurons： In control group, the numbers of Fos-IR neurons in ventrolateral part of PAG in simulated weightlessness group were obviously lower than succinylcholine-pretreatment group, but obviously higher than succinylcholine-injection group （46.94±3.38, 71.06±8.96 and 35.04±4.62, respectively, P 〈 0.05）. In 14-day simulated weightlessness group, the numbers of Fos-IR neurons in electrostimulation group were also obviously lower than succinylcholine-pretreatment group, and obviously higher than succinylcholine-injection group （27.77±3.27, 32.91±2.99 and 11.75±1.00, respectively, P 〈 0.05）. The numbers of Fos-IR neurons in all subgroups in control group were obviously higher than those subgroups in simulated weightlessness group. Compared with electrostimulation group, the percentage of expression of Fos in ventrolateral part of PAG responsed to nociceptive stimulus after administration of succinylcholine （SCH） was increased to 51.83% in control group and 18.51% in simulated weightlessness group.CONCLUSION ：① The expression of Fos in neurons in ventrolateral part of PAG were increased by the pretreatment of SCH before nociceptive stimulus.② Nociceptive stimulus could increase the expression of Fos in neurons in ventrolateral part of PAG. ③ The numbers of Fos-IR neurons in ventrolateral part of PAG were decreased obviously after 2-week simulated weightlessness.
文摘AIM:To analyze visual dysfunction in rats under simulated weightlessness(SW)by examining trans-laminar cribrosa pressure difference(TLCPD)and neuroimmune responses.METHODS:The 72 male Sprague-Dawley rats were randomly assigned into two groups(ground control and hindlimb unloading-simulated microgravity)using stratified randomization,with each group further subdivided into three exposure durations:SW 2-week(SW-2W),4-week(SW-4W),and 8-week(SW-8W),n=12 per subgroup.At the designated time points for each group,intraocular pressure(IOP)and intracranial pressure(ICP)were measured,and the trans-laminar cribrosa pressure difference(TLCPD)was calculated.Additionally,optomotor response(OMR),electroretinography(ERG),and optical coherence tomography(OCT)were performed.The number of retinal ganglion cells(RGCs)was quantified via immunofluorescence,the activation of astrocytes and microglial cells was determined,and Sholl analysis was conducted to assess the function and morphology of microglial cells.Data were analyzed with SPSS and GraphPad Prism(P<0.05).RESULTS:Under prolonged simulated microgravity,rats exhibited a progressive increase in both IOP and ICP,with the most pronounced rise observed at 8wk.Concurrently,the TLCPD shifted from a negative value in controls to a positive value.These pressure alterations were associated with retinal dysfunction,as evidenced by significant reductions in ERG b-wave and photopic negative response(PhNR)amplitudes.OCT and histological analyses revealed subtle photoreceptor layer damage:while the inner nuclear layer(INL)thickness remained relatively unchanged,the outer nuclear layer(ONL)thinned significantly,and the nerve fiber layer-ganglion cell layer complex thickness(NFL-GCL)complex initially thickened before later thinning.Immunofluorescence further demonstrated marked neuroimmune activation,with astrocytes transitioning from having large cell bodies with small,elongated,sparse processes to a phenotype characterized by compact,enlarged nuclei and aggregated processes,alongside notable RGC loss.CONCLUSION:Based on the results from the simulated microgravity rat model,microgravity-induced changes in dual-chamber pressure,and neuroimmune responses in the retina may play a key role in visual dysfunction.Specifically,the activation of retinal neuroimmune cells(astrocytes and microglial cells)induced by mechanical stress appears to be central to retinal and optic nerve damage.
文摘Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive thyroid-related cell lines cultured under simulated microgravity.Methods:Five thyroid-related cell lines—normal thyrocytes(Nthy-ori 3-1),papillary thyroid cancer(PTC)cells(SNU-790,TPC-1),poorly differentiated thyroid cancer cell(BCPAP),and anaplastic thyroid cancer cell(SNU-80)—were cultured under simulated microgravity(10-3 g)using a clinostat.Differentially expressed genes(DEGs)were analyzed using cDNA microarray,followed by functional annotation and assessment of aggressiveness via Transwell migration and invasion assays.Results:DEG analysis under simulated microgravity revealed distinct gene expression profiles by gravity condition,with 2980 DEGs in SNU-790,1033 in BCPAP,562 in TPC-1,477 in Nthy-ori 3-1,and 246 in SNU-80,as confirmed by hierarchical clustering.In PTC cell lines(SNU-790,TPC-1),G2–M phase–related genes were upregulated.In non-PTC cell lines(BCPAP,SNU-80),genes associated with innate immune response,Toll-like receptor signaling,were upregulated,whereas Hypoxia-Inducible Factor 1-alpha(HIF-1α)signaling-related genes were downregulated.Additionally,under simulated microgravity,significant migration was observed in SNU-790(3×104 cells)and BCPAP(2×104 and 3×104),while significant invasion occurred in SNU-790,Nthy-ori 3-1,and BCPAP at a seeding density of 2×104.Other conditions showed no significant differences.Conclusion:This study comprehensively evaluates the effects of simulated microgravity using a diverse panel of thyroid-related cell lines.Thesefindings provide valuable insight into how microgravity could influence cancer biology,emphasizing the importance of further research on cancer behavior in space environments and its implications for human health during long-term space missions.
基金the Chinese Manned Space Flight Projectthe National Natural Science Foundation of China (No.81571845)the Key Project of Logistics Research (No.BWS14C024).
文摘The Chinese space station will be built around 2020. As a national space laboratory, it will offer unique opportunities for studying the physiological effects of weightlessness and the efficacy of the countermeasures against such effects. In this paper, we described the development of countermeasure systems in the Chinese space program. To emphasize the need of the Chinese space program to implement its own program for developing countermeasures, we reviewed the literature on the negative physiological effects of weightlessness, the challenges of completing missions, the development of countermeasure devices, the establishment of countermeasure programs, and the efficacy of the countermeasure techniques in American and Russian manned spaceflights. In addition, a brief overview was provided on the Chinese research and development on countermeasures to discuss the current status and goals of the development of countermeasures against physiological problems associated with weightlessness.
