Effects of simulated microgravity on oxidative and anti-oxidative stress levels of carotid arteries in rats
10.3760/cma.j.cn11385420240506-00070
- VernacularTitle:模拟失重对大鼠颈动脉氧化应激与抗氧化应激水平的影响
- Author:
Qianqian YANG
1
;
Qiguang WANG
;
Sichen WANG
;
Yue WU
;
Yan ZHANG
;
Yunfan HAN
;
Zhongchao WANG
Author Information
1. 北部战区总医院全军心血管病研究所先心病内科，沈阳 110016
- Publication Type:Journal Article
- Keywords:
Weightlessness simulation;
Carotid artery;
Oxidative stress;
Anti-oxidative stress;
Keap-1/Nrf2 signaling pathway
- From:
Chinese Journal of Aerospace Medicine
2024;35(4):241-248
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of simulated microgravity on carotid oxidative stress and anti-oxidative stress in rats by using a rat tail-suspension model to simulate the hemodynamic changes caused by microgravity.Methods:Twelve healthy adult male Sprague-Dawley rats were completely randomized into control group and simulated suspension group, with 6 rats in each group. The rats in control group were fed in standard laboratory environment and could move freely. The feeding environment of the simulated suspension group rats was the same as that of the control group, and the tail suspension was maintained for 4 weeks. The differentially expressed genes in carotid tissue were obtained by transcriptome sequencing, and analyzed by volcano plot, Venn diagram and heatmap. The differentially expressed genes were further analyzed by Gene Ontology and the Kyoto encyclopedia of genes and genomes. Dihydroethidium staining was used to detect the content of reactive oxygen species in rat carotid artery. Western blotting was used to detect the expression changes of pro-oxidative stress factor nicotinamide adenine dinucleotide phosphate oxidase 4 and anti-oxidative stress factors Kelch-like ECH-associated protein-1, nuclear factor-E2 related factor 2, heme oxygenase-1, and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1 in each group. The contents/activities of malondialdehyde, superoxide dismutase, catalase, reduced glutathione and oxidized glutathione in each group were detected using the thiobarbituric acid method, 4-[2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate sodium method and colorimetry.Results:Compared with the rats in control group, the wet weight of soleus muscle and the ratio of the wet weight of soleus muscle to body weight in simulated suspension group rats were decreased ( t=19.98, 17.34, both P<0.001), and the differences were significant. Eighty differentially expressed genes related to oxidative stress were screened by transcriptional sequencing (52 up-regulated and 28 down-regulated), which were closely related to vascular remodeling pathways, including cyclic guanosine monophosphate-protein kinase G signal pathway, mitogen-activated protein kinase signal pathway, phosphoinositide 3-kinase-Akt signal pathway, protein processing in endoplasmic reticulum and lipid metabolism and atherosclerosis-related signal pathways. These genes were mainly involved in response to antioxidant defense, chaperone-mediated autophagy, stress fiber, contractile actin filament bundle, actin filament bundle, growth factor activity, chaperone binding and cytokine activity. Compared with the control group, the levels of reactive oxygen species ( t=3.83, P=0.028) and malondialdehyde ( t=8.75, P<0.001) in the simulated suspension group were significantly increased. The protein expression of nicotinamide adenine dinucleotide phosphate oxidase 4 ( t=11.49 , P<0.001) was significantly increased, with statistical significance. The activities of antioxidant stress related factors superoxide dismutase ( t=6.44, P=0.001), catalase ( t=6.83, P=0.001), and the ratio of reduced glutathione to oxidized glutathione ( t=3.46, P=0.003), and nuclear factor-E2 related factor 2 ( t=28.18, P<0.001), heme oxygenase-1 ( t=8.03, P<0.001), and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1 ( t=9.71, P<0.001) were significantly decreased, the protein expression of Kelch-like ECH-associated protein-1 ( t=5.06, P<0.001) was increased, and the differences were statistically significant. Conclusions:Simulated microgravity can enhance the level of carotid oxidative stress in rats, including promoting the expression of pro-oxidative stress-related factors and suppressing the activity of anti-oxidative stress pathways. Their combined action will lead to the oxidative stress injury of carotid arteries. This process may be one of the key mechanisms involved in the remodeling of arterial structure and function induced by simulated microgravity.
