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Responses of Intestinal Mucosal Barrier Functions of Rats to Simulated Weightlessness.

ABSTRACT: Exposure to microgravity or weightlessness leads to various adaptive and pathophysiological alterations in digestive structures and physiology. The current study was carried out to investigate responses of intestinal mucosal barrier functions to simulated weightlessness, by using the hindlimb unloading rats model. Compared with normal controls, simulated weightlessness damaged the intestinal villi and structural integrity of tight junctions, up-regulated the expression of pro-apoptotic protein Bax while down-regulated the expression of anti-apoptotic protein Bcl-2, thus improved the intestinal permeability. It could also influence intestinal microbiota composition with the expansion of Bacteroidetes and decrease of Firmicutes. The predicted metagenomic analysis emphasized significant dysbiosis associated differences in genes involved in membrane transport, cofactors and vitamins metabolism, energy metabolism, and genetic information processing. Moreover, simulated weightlessness could modify the intestinal immune status characterized by the increase of proinflammatory cytokines, decrease of secretory immunoglobulin A, and activation of TLR4/MyD88/NF-?B signaling pathway in ileum. These results indicate the simulated weightlessness disrupts intestinal mucosal barrier functions in animal model. The data also emphasize the necessity of monitoring and regulating astronauts' intestinal health during real space flights to prevent breakdowns in intestinal homeostasis of crewmembers.

SUBMITTER: Jin M

PROVIDER: S-EPMC6011188 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Responses of Intestinal Mucosal Barrier Functions of Rats to Simulated Weightlessness.

Jin Mingliang M Zhang Hao H Zhao Ke K Xu Chunlan C Shao Dongyan D Huang Qingsheng Q Shi Junling J Yang Hui H

Frontiers in physiology 20180614

Exposure to microgravity or weightlessness leads to various adaptive and pathophysiological alterations in digestive structures and physiology. The current study was carried out to investigate responses of intestinal mucosal barrier functions to simulated weightlessness, by using the hindlimb unloading rats model. Compared with normal controls, simulated weightlessness damaged the intestinal villi and structural integrity of tight junctions, up-regulated the expression of pro-apoptotic protein B ...[more]

PMID: 29962963

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Project description:Background: Our studies demonstrated that the space environment has an impact on the brain function of astronauts. Numerous ground-based microgravity and social isolation showed that the space environment can induce brain function damages in humans and animals. Dammarane sapogenins (DS), an active fraction from oriental ginseng, possesses neuropsychic protective effects and has been shown to improve depression and memory. This study aimed to explore the effects and mechanisms of DS in attenuating depressive-like behaviors and cognitive deficiency induced by simulated weightlessness and isolation [hindlimb suspension and isolation (HLSI)] in rats. Methods: Male rats were orally administered with two different doses of DS (37.5, 75 mg/kg) for 14 days, and huperzine-A (1 mg/kg) served as positive control. Rats were subjected to HLSI for 14 days except the control group during drug administration. The depressive-like behaviors were then evaluated by the open-field test, the novel object recognition test, and the forced swimming test. The spatial memory and working memory were evaluated by the Morris water maze (MWM) test, and the related mechanism was further explored by analyzing the activity of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and superoxide dismutase (SOD) in the hippocampus of rats. Results: The results showed that DS treatment significantly reversed the HLSI-induced depressive-like behaviors in the open-field test, the novel object recognition test, and the forced swimming test and improved the HLSI-induced cognitive impairment in the MWM test. Furthermore, after DS treatment, the ChAT and SOD activities of HLSI rats were increased while AChE activity was significantly suppressed. Conclusions: These findings clearly demonstrated that DS might exert a significant neuropsychic protective effect induced by spaceflight environment, driven in part by the modulation of cholinergic system and anti-oxidation in the hippocampus.

Project description:Low molecular seleno-aminopolysaccharide (LSA) was synthesized with sodium selenite and low molecular aminopolysaccharide (LA), which is an organic selenium compound. This study is aimed to investigate the protective effect of LSA on the intestinal mucosal barrier in weaning stress rats by detecting the intestinal tissue morphology and function, mucosal thickness and permeability, the structure of MUC2, antioxidant index, the expression level of intracellular transcription factor NF-E2-related factor 2 (Nrf2), and its related factors. The results showed that LSA significantly increased the height of intestinal villi (p < 0.05) and increased the thickness of intestinal mucosa and the number of goblet cells, which indicated that LSA has a protective effect on the intestinal mucosal barrier that is damaged by weaning. Moreover, LSA significantly reduced the level of DAO, D-LA, and LPS compared with the weaning group (p < 0.05), which indicated that LSA reduced the intestinal damage and permeability of weaning rats. In addition, LSA could increase the number and length of glycans chains and the abundance of acid glycans structures in the MUC2 structure, which indicated that LSA alleviated the changes of intestinal mucus protein structure. LSA significantly increased the levels of GSH-Px, SOD, LDH, and CAT, while it decreased the level of MDA in serum and intestinal tissue, which suggested that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress of weaning rats. RT-PCR results showed that LSA significantly increased the expression level of antioxidant genes (GSH-Px, SOD, Nrf2, HO-1), glycosyltransferase genes (GalNT1, GalNT3, GalNT7) and mucin gene (MUC2) in intestinal mucosa (p < 0.05). The results of western blot showed that the LSA activated the Nrf2 signaling pathway by down-regulating the expression of Keap1and up-regulating the expression of Nrf2, and protected the intestinal mucosa from oxidative stress. Overall, LSA could play a protective role in intestinal mucosal barrier of weaning rats by activating the Nrf2 pathway and alleviating the alnormal change of mucin MUC2.

Project description:AimThe herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model.MethodsA rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1? and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier.ResultsPI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1? and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1? and IL-4.ConclusionChang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

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Responses of Intestinal Mucosal Barrier Functions of Rats to Simulated Weightlessness.

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Responses of Intestinal Mucosal Barrier Functions of Rats to Simulated Weightlessness.

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