Role of endoplasmic reticulum stress in omega-3 polyunsaturated fatty acids supplementation for attenu-ating inflammatory response in experimental rat models of colitis / 中华临床营养杂志

ABSTRACT

Objective To investigate the effects and mechanisms of omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation on colonic macroscopic and histological score , inflammatory response , and endo-plasmic reticulum stress ( ERS ) response in experimental rat models of colitis .Methods Experimental rat models of colitis were induced by trinitro-benzene-sulfonic acid (TNBS).Totally 100 male SD rats were ran-domly divided into 5 groups according to the random data tablessham operation group ( Sham group ) , inflam-matory bowel disease group (IBD group),ω-3 PUFA supplementation group (IBD+ω-3 group), 5-aminosali-cylic acid group ( IBD +5-ASA group ) , and ERS activation 2-deoxy-D-glucose group ( IBD +ω-3 +2-DG group).Colonic macroscopic and histological scores were evaluated on days 1, 3, 7 and 14 after modeling.The serum levels of tumor necrosis factor-α(TNF-α), interleukin (IL) -1, and IL-6 were measured using en-zyme-linked immunosorbent assay , whereas ERS cytokines including glucose-regulated protein 78 ( GRP78 ) , inositol-requiring enzyme 1 (IRE-1), and C/EBP homologous protein (CHOP) were tested by Western blot. Results Compared with the Sham group , colonic macroscopic and histological score , the serum levels of in-flammation relatived factors (TNF-α, IL-1, IL-6) and ERS relatived factors (GRP78、 IRE-1, CHOP) were significantly increased on the rest of the four groups ( all P<0.001 ) .Compared with the IBD group , ω-3 PUFA supplementation reduced colonic macroscopic [7 d 3.55 ±0.29 vs.4.37 ±0.39, P=0.03, 14 d2.46 ±0.17 vs.3.86 ±0.21, P=0.04] and histological score [7 d (2.56 ±0.27) scores vs.(3.45 ± 0.40) scores, P=0.02, 14 d (2.23 ±0.20) scores vs.(3.06 ±0.26) scores, P=0.04].Meanwhile,ω-3 PUFA supplementation suppressed the expressions of inflammation [TNF-α(43.71 ±11.39) pg/ml vs. (84.97 ±13.81) pg/ml, P=0.02, IL-1(38.51 ±10.60) pg/ml vs.(73.04 ±12.48) pg/ml, P=0.01, IL-6(28.91 ±7.27) pg/ml vs.(53.45 ±9.40) pg/ml, P=0.02] and ERS relatived factors (GRP782.41 ±0.29 vs.1.47 ±0.21, P=0.01, IRE-12.83 ±0.31 vs.1.23 ±0.20, P<0.001, CHOP1.89 ± 0.17 vs.1.32 ±0.11 , P=0.04 ) .However , the salutary effects of ω-3 PUFA would been reversed by ERS activation 2-deoxy-D-glucose [ TNF-α (72.67 ±10.37 ) pg/ml vs.(43.71 ±11.39 ) pg/ml, P =0.02, IL-1(57.66 ±13.88) pg/ml vs.(38.51 ±10.60) pg/ml, P=0.02, IL-6 (46.10 ±9.67) pg/ml vs. (28.91 ±7.27) pg/ml, P=0.01, GRP781.47 ±0.21 vs.1.82 ±0.24, P=0.03, IRE-11.23 ±0.20 vs.2.21 ±0.23, P=0.02, CHOP1.32 ±0.11 vs.1.61 ±0.16, P=0.04].Conclusion The salutary effects of ω-3 PUFA supplementation on the colitis induced by TNBS appear to be mediated by inhibited inflam -matory responses , which may suppress the activation of ERS response .