Protective effect of glutamine on intestinal injury and bacterial community in rats exposed to hypobaric hypoxia environment.
OBJECTIVE
To investigate the protective effect of glutamine (Gln) on intestinal injury and the bacterial community in rats exposed to hypobaric hypoxia environment.


METHODS
Sprague-Dawley rats were divided into control, hypobaric hypoxia (HH), and hypobaric hypoxia + Gln (5.0 g/kg BW·d) (HG) groups. On the first 3 d, all rats were placed in a normal environment. After the third day, the HH and HG groups were transferred into a hypobaric chamber at a simulated elevation of 7000 m for 5 d. The rats in the HG group were given Gln by gavage daily for 8 d. The rats in the control and HH groups were treated with the same volume of saline. The intestinal morphology, serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ) and diamino oxidase (DAO) were examined. We also evaluated the expression levels of occludin, toll-like receptor 4 (TLR4), nuclear factor-κB p65 (NF-κB p65) and myeloid differentiation factor 88 (MyD88), and examined the bacterial community in caecal contents.


RESULTS
Hypobaric hypoxia induced the enlargement of the heart, liver, lung and kidney, and caused spleen atrophy. Intestinal villi damage was also observed in the HH group. Supplementation with Gln significantly alleviated hypobaric-induced damage to main organs including the intestine, increased serum SOD (1.14 ± 0.03 vs 0.88 ± 0.04, P < 0.05) and MDA (8.35 ± 1.60, P < 0.01) levels and decreased serum IL-6 (1172.13±30.49 vs 1407.05 ± 34.36, P < 0.05), TNF-α (77.46 ± 0.78 vs 123.70 ± 3.03, P < 0.001), IFN-γ (1355.42 ± 72.80 vs 1830.16 ± 42.07, P < 0.01) and DAO (629.30 ± 9.15 vs 524.10 ± 13.34, P < 0.001) levels. Moreover, Gln significantly increased occludin (0.72 ± 0.05 vs 0.09 ± 0.01, P < 0.001), TLR4 (0.15 ± 0.05 vs 0.30 ±0.09, P < 0.05), MyD88 (0.32 ± 0.08 vs 0.71 ± 0.06, P < 0.01), and NF-κB p65 (0.16 ± 0.04 vs 0.44 ± 0.03, P < 0.01) expression levels and improved the intestinal bacterial community.


CONCLUSIONS
Gln treatment protects from intestinal injury and regulates the gut flora imbalance in hypoxia environment. These effects may be related to the TLR4/MyD88/NF-κB signaling pathway.
Chun-Lan Xu, Rui Sun, Xiang-Jin Qiao, Cui-Cui Xu, Xiao-Ya Shang, Wei-Ning Niu, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China.
Chun-Lan
CL
Xu
Chun-Lan Xu, Rui Sun, Xiang-Jin Qiao, Cui-Cui Xu, Xiao-Ya Shang, Wei-Ning Niu, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China.
Rui
R
Sun
Chun-Lan Xu, Rui Sun, Xiang-Jin Qiao, Cui-Cui Xu, Xiao-Ya Shang, Wei-Ning Niu, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China.
Xiang-Jin
XJ
Qiao
Chun-Lan Xu, Rui Sun, Xiang-Jin Qiao, Cui-Cui Xu, Xiao-Ya Shang, Wei-Ning Niu, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China.
Cui-Cui
CC
Xu
Chun-Lan Xu, Rui Sun, Xiang-Jin Qiao, Cui-Cui Xu, Xiao-Ya Shang, Wei-Ning Niu, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China.
Xiao-Ya
XY
Shang
Chun-Lan Xu, Rui Sun, Xiang-Jin Qiao, Cui-Cui Xu, Xiao-Ya Shang, Wei-Ning Niu, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China.
Wei-Ning
WN
Niu
D000818:Animals; D001419:Bacteria / Q000145:classification / Q000187:drug effects* / Q000254:growth & development; D016207:Cytokines / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D005973:Glutamine / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000097:blood; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; C498145:Rela protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D005973:Glutamine; D008315:Malondialdehyde; D013482:Superoxide Dismutase
Bacterial community; Glutamine; Hypobaric hypoxia; Immunomodulation; Intestinal mucosa