Modulation of hypoxia-inducible factor-1

Autor: Changyou, Fan, Jie, Han, Xianjun, Liu, Fei, Zhang, Yingshan, Long, Qitao, Xie
Rok vydání: 2019
Předmět:
Zdroj: The British journal of nutrition. 122(6)
ISSN: 1475-2662
Popis: Intestinal barrier inflammatory damage is commonly accompanied by hypoxia. The hypothesis that dietary Acanthopanax senticosus polysaccharides (ASPS) might modulate the hypoxia-inducible factor-1α (HIF-1α) signalling pathway and contribute to attenuate intestinal injury was tested in lipopolysaccharide (LPS)-challenged piglets. Thirty-six weaned pigs were randomly allocated to one of the following three groups: (1) basal diet + saline challenge; (2) basal diet + LPS challenge; (3) basal diet with 800 mg/kg ASPS + LPS challenge. LPS was injected at 15, 18 and 21 d, and intestinal sections were sampled following blood collection at 21 d . The results showed ASPS reversed (P0·05) LPS-induced decrease in average daily feed intake and rise (P0·05) of diarrhoea incidence and index. Biochemical index reflecting gut barrier damage and function involving ileal pro-inflammatory cytokines (TNF-α and IL-1β) and enzyme activity (diamine oxidase and lactase), as well as circulatory d-xylose, was normalised (P0·05) in LPS-challenged piglets receiving ASPS. ASPS also ameliorated intestinal morphological deterioration of LPS-challenged piglets, proved by elevated ileal villus height (P0·05) and improved appearance of epithelial villus and tight junction ultrastructure. Moreover, ASPS prevented LPS-induced amplification of inflammatory mediators, achieved by depressed ileal mRNA abundance of TNF-α, inducible NO synthase and IL-1β concentration. Importantly, ileal protein expressions of HIF-1α, cyclo-oxygenase-2 (COX-2) and NFκB p65 were also suppressed with ASPS administration (P0·05). Collectively, these results suggest the improvement of mucosal inflammatory damage and diarrhoea in immune stress piglets is possibly associated with a novel finding where HIF-1α/COX-2 pathway down-regulation is involved in NFκB p65-inducible releasing of inflammatory cytokines by dietary ASPS.
Databáze: OpenAIRE