[Effects of high +Gx during simulated spaceship emergency return on learning and memory in rats].
Xu Zhi-peng,Sun Xi-qing,Liu Ting-song,Wu Bin,Zhang Shu,Wu Ping
Hang tian yi xue yu yi xue gong cheng = Space medicine & medical engineering
OBJECTIVE:To observe the effects of high +Gx during simulated spaceship emergency return on learning and memory in rats. METHOD:Thirty two male SD rats were randomly divided into control group, 7 d simulated weightlessness group, +15 Gx/180 s group and +15 Gx/180 s exposure after 7 d simulated weightlessness group, with 8 rats in each group. The changes of learning and memory in rats were measured after stresses by means of Y-maze test and step-through test. RESULT:In Y-maze test, as compared with control group, percentage of correct reactions decreased significantly (P<0.01) and reaction time increased significantly (P<0.01) in hypergravity after simulated weightlessness group at all time after stress; as compared with +15 Gx group or simulated weightlessness group, percentage of correct reactions decreased significantly (P< 0.05) and reaction time increased significantly (P< 0.05) immediately after stress. In step-through test, as compared with control group, total time increased significantly (P<0.01) in hypergravity after simulated weightlessness group at 1 d after stress; latent time decreased significantly (P<0.01) and number of errors increased significantly (P< 0.01) at all the time after stress. As compared with +15 Gx group, total time increased significantly (P<0.05) immediately, 1 d after stress. As compared with simulated weightlessness group, total time and number of errors increased significantly (P<0.05) immediately after stress. CONCLUSION:It is suggested that +15 Gx/180 s and simulated weightlessness may affect the ability of learning and memory of rats. Simulated weightlessness for 7 d can aggravate the effect of +Gx on learning and memory ability in rats.
Microgravity-induced changes in aortic stiffness and their role in orthostatic intolerance.
Tuday Eric C,Meck Janice V,Nyhan Daniel,Shoukas Artin A,Berkowitz Dan E
Journal of applied physiology (Bethesda, Md. : 1985)
Microgravity (microG)-induced orthostatic intolerance (OI) in astronauts is characterized by a marked decrease in cardiac output (CO) in response to an orthostatic stress. Since CO is highly dependent on venous return, alterations in the resistance to venous return (RVR) may be important in contributing to OI. The RVR is directly dependent on arterial compliance (C(a)), where aortic compliance (C(ao)) contributes up to 60% of C(a). We tested the hypothesis that microG-induced changes in C(a) may represent a protective mechanism against OI. A retrospective analysis on hemodynamic data collected from astronauts after 5- to 18-day spaceflight missions revealed that orthostatically tolerant (OT) astronauts showed a significant decrease in C(a) after spaceflight, while OI astronauts showed a slight increase in C(a). A ground-based animal model simulating microG, hindlimb-unweighted rats, was used to explore this phenomenon. Two independent assessments of C(ao), in vivo pulse wave velocity (PWV) of the thoracic aorta and in vitro pressure-diameter squared relationship (PDSR) measurements of the excised thoracic aorta, were determined. PWV showed a significant increase in aortic stiffness compared with control, despite unchanged blood pressures. This increase in aortic stiffness was confirmed by the PDSR analysis. Thus both actual microG in humans and simulated microG in rats induces changes in C(ao). The difference in C(a) in OT and OI astronaut suggests that the microG-induced decrease in C(a) is a protective adaptation to spaceflight that reduces the RVR and allows for the maintenance of adequate CO in response to an orthostatic stress.
[Change of pulmonary circulation in microgravity and simulated microgravity].
Sun L,Xiang Q L,Wang D S,Ren W
Hang tian yi xue yu yi xue gong cheng = Space medicine & medical engineering
Fluid is transferred cephalad in microgravity and simulated microgravity, and the pulmonary circulation is the first to be affected. Blood and fluid contents in the lungs increase, but unevenly distributed among various zones of the lungs. Blood vessels in the lungs are filled and distend. Capillary changes have been observed in the animal model of simulated microgravity. Studies about the changes of regulative function of pulmonary circulation are relatively rare. Observations of the reactivity of pulmonary vessels may help to understand the mechanisms of the changes in pulmonary circulation during microgravity.
Simulated microgravity exposure modulates the phenotype of cultured vascular smooth muscle cells.
Kang Hongyan,Fan Yubo,Sun Anqiang,Jia Xiaoling,Deng Xiaoyan
Cell biochemistry and biophysics
Evidence from ground-based animal studies using tail-suspended hindlimb unloaded rats model has clearly demonstrated that simulated microgravity-induced smooth muscle cell phenotype conversion, a characteristic vascular structural and functional remodeling, may be one of the key contributors to postspaceflight orthostatic intolerance. However, the rats model involves multiple collective effects of microgravity including cephalic fluid shift and postural muscle unloading on smooth muscle cells (SMCs). It cannot isolate a single factor from the collective ones and therefore is not ideal to study the effects of gravitational vector alteration alone on SMCs. To test the hypothesis that gravitational vector alteration per se might affect smooth muscle cell phenotype, a roller culture apparatus was employed to expose cultured rat aortic smooth muscle cells (RASMCs) to simulated microgravity. Cell proliferation, cell cycle distribution, apoptosis, migration, and nitric oxide production rates were measured and compared between the control and the simulated microgravity groups. Cell cytoskeleton reorganization induced by simulated microgravity was observed by confocal microscopy. Specific contractile and synthetic Gene expression at the mRNA level was quantified by reverse transcriptional polymerase chain reaction. It was observed that simulated microgravity suppressed RASMC proliferation and migration, enhanced cell apoptosis, stimulated NO release, and destroyed the original well-organized cytoskeleton. Moreover, at the mRNA level, long-time exposure (≥ 72 h) to simulated microgravity induced a contractile phenotype tendency by up-regulating smMHC expression. All these findings suggest that the phenotype modulation of vascular smooth muscle cells may be gravity dependent.
Simulated microgravity promotes monocyte adhesion to rat aortic endothelium via nuclear factor-κB activation.
Liu Huan,Wang Zhong-Chao,Bai Yun-Gang,Cai Yue,Yu Jin-Wen,Zhang Hai-Jun,Bao Jun-Xiang,Ren Xin-Ling,Xie Man-Jiang,Ma Jin
Clinical and experimental pharmacology & physiology
Microgravity-induced vascular remodelling may play an important role in post-spaceflight orthostatic intolerance. In this study, we aimed to investigate the effects of simulated microgravity on monocyte adhesion to aortic endothelium in hindlimb unweighted rats and to elucidate the underlying mechanisms associated with this event. Sprague-Dawley rats were subjected to 4-week hindlimb unweighting to simulate microgravity. The recruitment of monocytes to the abdominal aorta was investigated by en face immunofluorescence staining and monocyte binding assays. The expression of the adhesion molecules E-selectin and vascular cell adhesion molecule-1 as well as the cytokine monocyte chemoattractant protein (MCP)-1 was evaluated by immunohistochemical staining, western blot, and quantitative reverse transcription polymerase chain reaction analyses. Additionally, nuclear factor-κB (NF-κB) activation and the messenger RNA expression levels of E-selectin, vascular cell adhesion molecule-1, and MCP-1 were assessed with the administration of an NF-κB inhibitor, pyrrolidine dithiocarbamate. Results showed that simulated microgravity significantly increased monocyte recruitment to the aortic endothelium, protein expression of E-selectin and MCP-1, and NF-κB activation in the abdominal aorta of rats. Pyrrolidine dithiocarbamate treatment not only significantly inhibited NF-κB activity but also reduced the messenger RNA levels of E-selectin, vascular cell adhesion molecule-1, and MCP-1 as well as monocyte recruitment in the abdominal aorta of hindlimb unweighted rats. These results suggest that simulated microgravity increases monocyte adhesion to rat aortic endothelium via the NF-κB-mediated expression of the adhesion molecule E-selectin and the cytokine MCP-1. Therefore, an NF-κB-mediated inflammatory response may be one of the cellular mechanisms responsible for arterial remodelling during exposure to microgravity.
Effects of real and simulated weightlessness on the cardiac and peripheral vascular functions of humans: A review.
Zhu Hui,Wang Hanqing,Liu Zhiqiang
International journal of occupational medicine and environmental health
Weightlessness is an extreme environment that can cause a series of adaptive changes in the human body. Findings from real and simulated weightlessness indicate altered cardiovascular functions, such as reduction in left ventricular (LV) mass, cardiac arrhythmia, reduced vascular tone and so on. These alterations induced by weightlessness are detrimental to the health, safety and working performance of the astronauts, therefore it is important to study the effects of weightlessness on the cardiovascular functions of humans. The cardiovascular functional alterations caused by weightlessness (including long-term spaceflight and simulated weightlessness) are briefly reviewed in terms of the cardiac and peripheral vascular functions. The alterations include: changes of shape and mass of the heart; cardiac function alterations; the cardiac arrhythmia; lower body vascular regulation and upper body vascular regulation. A series of conclusions are reported, some of which are analyzed, and a few potential directions are presented.
The ICAM-1 expression level determines the susceptibility of human endothelial cells to simulated microgravity.
Buravkova Ludmila B,Rudimov Eugene G,Andreeva Elena R,Grigoriev Anatoly I
Journal of cellular biochemistry
Microgravity is a principal risk factor hampering human cardiovascular regulation during space flights. Endothelial dysfunction associated with the impaired integrity and uniformity of the monolayer represents a potential trigger for vascular damage. We characterized the expression profile of the multi-step cascade of adhesion molecules (ICAM-1, VCAM-1, E-selectin, VE-cadherin) in umbilical cord endothelial cells (ECs) after 24 h of exposure to simulated microgravity (SMG), pro-inflammatory cytokine TNF-α, and the combination of the two. Random Positioning Machine (RPM)-mediated SMG was used to mimic microgravity effects. SMG stimulated the expression of E-selectin, which is known to be involved in slowing leukocyte rolling. Primary ECs displayed heterogeneity with respect to the proportion of ICAM-1-positive cells. ECs were divided into two groups: pre-activated ECs displaying high proportion of ICAM-1 -cells (ECs-1) (greater than 50%) and non-activated ECs with low proportion of ICAM-1 -cells (ECs-2) (less than 25%). Only non-activated ECs-2 responded to SMG by elevating gene transcription and increasing ICAM-1 and VE-cadherin expression. This effect was enhanced after cumulative SMG-TNF-α exposure. ECs-1 displayed an unexpected decrease in number of E-selectin- and ICAM-1-positive ECs and pronounced up-regulation of VCAM1 upon activation of inflammation, which was partially abolished by SMG. Thus, non-activated ECs-2 are quite resistant to the impacts of microgravity and even exhibited an elevation of the VE-cadherin gene and protein expression, thus improving the integrity of the endothelial monolayer. Pre-activation of ECs with inflammatory stimuli may disturb the EC adhesion profile, attenuating its barrier function. These alterations may be among the mechanisms underlying cardiovascular dysregulation in real microgravity conditions.
Effect of miR-27b-5p on apoptosis of human vascular endothelial cells induced by simulated microgravity.
Pan Yi-Kai,Li Cheng-Fei,Gao Yuan,Wang Yong-Chun,Sun Xi-Qing
Apoptosis : an international journal on programmed cell death
Weightlessness-induced cardiovascular dysfunction can lead to physiological and pathological consequences. It has been shown that spaceflight or simulated microgravity can alter expression profiles of some microRNAs (miRNAs). Here, we attempt to identify the role of miRNAs in human umbilical vein endothelial cells (HUVECs) apoptosis under simulated microgravity. RNA-sequencing and quantitative real-time PCR (qRT-PCR) assays were used to identify differentially expressed miRNAs in HUVECs under simulated microgravity. Then we obtained the target genes of these miRNAs through target analysis software. Moreover, GO and KEGG enrichment analysis were performed. The effects of these miRNAs on HUVECs apoptosis were evaluated by flow cytometry, Western blot and Hoechst staining. Furthermore, we obtained the target gene of miR-27b-5p by luciferase assay, qRT-PCR and Western blot. Finally, we investigated the relationship between this target gene and miR-27b-5p in HUVECs apoptosis under normal gravity or simulated microgravity. We found 29 differentially expressed miRNAs in HUVECs under simulated microgravity. Of them, the expressions of 3 miRNAs were validated by qRT-PCR. We demonstrated that miR-27b-5p affected HUVECs apoptosis by inhibiting zinc fingers and homeoboxes 1 (ZHX1). Our results reported here demonstrate for the first time that simulated microgravity can alter the expression of some miRNAs in HUVECs and miR-27b-5p may protect HUVECs from apoptosis under simulated microgravity by targeting ZHX1.
Effects of miR-503-5p on apoptosis of human pulmonary microvascular endothelial cells in simulated microgravity.
Tang Na-Ping,Hui Tao-Tao,Ma Jing,Mei Qi-Bing
Journal of cellular biochemistry
Recent studies have shown that microRNA (miRNAs) can play important roles in the regulation of endothelial cell (EC) function. However, the expression profile of miRNAs and their effects on the apoptosis of ECs under microgravity conditions remains unclear. In this study, the apoptosis of human pulmonary microvascular endothelial cells (HPMECs) under simulated microgravity was identified by Annexin V and propidium iodide double staining and transmission electron microscopy. miRNA microarray assay was used to screen the differentially expressed miRNAs in HPMECs under simulated microgravity, and eight differentially expressed miRNAs were identified. Specifically, miR-503-5p, which was found to be most significantly upregulated in both microarray and quantitative reverse-transcription polymerase chain reaction assays, was selected for further functional investigation. Overexpression of miR-503-5p induced apoptosis of HPMECs under normal gravity and aggravated the negative effects of simulated microgravity on HPMECs. Furthermore, silencing of miR-503-5p expression effectively attenuated the negative effects of simulated microgravity on HPMECs. Further experiments showed that the mRNA and protein expression of anti-apoptotic factor B-cell lymphoma-2 (Bcl-2), which has been confirmed as a direct target of miR-503-5p, was inhibited by the upregulation of miR-503-5p and increased by the downregulation of miR-503-5p. Taken together, our findings demonstrate, for the first time, that miR-503-5p can induce apoptosis of HPMECs under simulated microgravity through, at least in part, inhibiting the expression of Bcl-2.
Effect of simulated microgravity and its associated mechanism on pulmonary circulation in rats.
Li Tian Zhi,Yuan Ming,Chen Zhen Hong,Guo Ying Hua,Kang Chun Yan,Wang Jing Yu,Li Zhi Li,Wang De Sheng,Wang Hui Juan,Yuan Min,Liu Chang Ting
Biomedical and environmental sciences : BES
OBJECTIVE:To study the effect of Simulated Microgravity and its Associated Mechanism on Pulmonary Circulation in Rats). METHODS:Rat tail-suspension model was used to simulate the physiological effects of microgravity and changes in pulmonary blood vessel morphology, pulmonary arterial and venous blood pressure, pulmonary vascular resistance, pulmonary vasomotoricity, as well as the regulation of pulmonary circulation by cytokines produced and released by the lung of rats were measured. RESULTS:The walls of pulmonary blood vessels of rats were thickened, and the pulmonary artery was reconstructed with increased pulmonary vascular resistance. The pulmonary blood vessels of rats became more prone to dilation as contractions increased. Rat epithelial Adrenomedulin gene transcription and protein expression were upregulated. The level of basic fibroblast growth Factor of rat was also elevated. CONCLUSION:Findings from the present study on rats revealed that the microgravity can affect pulmonary blood vessel structure, pulmonary arterial pressure, and pulmonary blood vessel self-regulation and cytokine production.