期刊
LIFE SCIENCES
卷 216, 期 -, 页码 168-175出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2018.11.048
关键词
Rhein; LPS; Intestinal barrier injury; Oxidative stress; Inflammation; MAPKs; Nrf2
资金
- National Natural Science Foundation of China [31472228]
Aims: In this study, we explored the underlying mechanisms of protective effects of rhein against intestinal barrier injury in a rat model, induced by intraperitoneal injection of lipopolysaccharide (LPS). Main methods: Twenty-four male rats were assigned equally to three groups. Rats were given an oral administration of rhein (66.7 mg/ kg/day) or not for three continuous days. LPS or saline were injected intraperitoneally in an hour after the last oral administration. The rats were sacrificed at 7 h after LPS or saline administration. Both blood samples and intestinal samples were collected. Key findings: Rhein pretreatment markedly inhibited the levels of serum diamine oxidase (DAO), D-lactate (D-lac) and intestinal histological damage, significantly recovered the levels of intestinal DAO, ZO-1 and occludin. Additionally, rhein suppressed LPS-induced intestinal inflammation and oxidative stress, by decreased serum and intestinal, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 and nitric oxide levels, up-regulated intestinal catalase, glutathione peroxidase (GSH-Px) activities and HO-1 expression, and down-regulated malondialdehyde (MDA) level in the small intestine. Finally, rhein inhibited JNK, p38 MAPK phosphorylation and activated Nrf2 pathway. Significance: Rhein could exert the anti-inflammatory and anti-oxidative effects against LPS-induced intestinal barrier injury by suppressing p38 MAPK and JNK and activating Nrf2 pathway.
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