Effect of ω-3 polyunsaturated fatty acids and ω-6 polyunsaturated acids on Toll-like receptor/nuclear factor-κB signaling pathway and the inflammatory cytokines in neonatal rats with brain injury induced by lipopolysaccharide

Abstract

Objective To investigate the effects of ω-3 polyunsaturated fatty acids(ω-3PUFAs) and ω-6 polyunsaturated fatty acids(ω-6PUFAs) on Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) signaling pathway, and the expressions of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in neonatal rats with brain injury induced by lipopolysaccharide (LPS). Methods Ninety-six neonatal rats were divided into control group, ω-3PUFAs group, ω-6PUFAs group, and LPS group by using random number table method. Intraperitoneal injection of LPS was performed in LPS group, ω-6PUFAs group and ω-3PUFAs group to establish models of rat brain injury.The rats in control group received 9 g/L saline.Twelve newborn rats were killed at 1 d or 5 d after intraperito-neal injection in each group for hippocampus selection. Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of TLR4, NF-κB, TNF-α, IL-1β and IL-6. Results One day after mode-ling, TLR4, NF-κB, TNF-α, IL-1β and IL-6 mRNA expressions in ω-3PUFAs group (10.63±0.07, 5.86±1.05, 7.65±2.29, 5.23±1.31, 3.36±0.72) were lower than those in ω-6PUFAs group (18.83±2.10, 8.79±2.08, 11.95±3.23, 10.97±2.24, 6.37±1.17) and LPS group (15.76±1.59, 7.13±1.10, 9.71±2.14, 7.83±0.85, 4.78±0.51), and the differences were all statistically significant(all P<0.05); which in ω-6PUFAs group were higher than those in LPS group, and the differences were all significant (all P<0.05). TLR4, NF-κB, TNF-α, IL-1β and IL-6 protein levels in ω-3PUFAs group (1.57±0.11, 1.58±0.09, 1.55±0.09, 1.63±0.31, 1.36±0.12) were lower than those in ω-6PUFAs group (1.96±0.17, 2.21±0.12, 1.95±0.23, 1.97±0.24, 1.77±0.17) and LPS group (1.73±0.15, 1.87±0.10, 1.79±0.14, 1.83±0.15, 1.58±0.11) in 1 d, and the diffe-rences were all significant (all P<0.05), and those in ω-6PUFAs group were higher than those in LPS group (all P<0.05). Similarly, TLR, NF-κB, TNF-α, IL-1β and IL-6 mRNA and protein expression levels in ω-3PUFAs group (3.78±0.88, 3.86±0.62, 6.26±1.94, 3.65±1.44, 2.11±0.87; 1.15±0.08, 1.32±0.10, 1.46±0.04, 1.38±0.14, 1.21±0.09) were lower than those in ω-6PUFAs group (7.76±1.65, 5.51±0.88, 7.96±2.13, 5.35±1.75, 4.88±1.35; 1.42±0.15, 1.51±0.36, 1.65±0.13, 1.72±0.23, 1.48±0.10) and LPS group (6.21±1.87, 4.98±0.73, 7.11±2.10, 4.84±1.75, 4.25±0.64; 1.35±0.13, 1.44±0.22, 1.59±0.10, 1.61±0.18, 1.35±0.07)in 5 d (all P<0.05), and which in ω-6PUFAs group were higher than those in LPS group, and the differences were significant (all P<0.05). Conclusion ω-6PUFAs can up-regulate the activity of TLR4, NF-κB, and reduce the release of TNF-α, IL-1β and IL-6; and ω-3PUFAs can down-regulate the activity of TLR4, NF-κB, and reduce the release of TNF-α, IL-1β and IL-6, so it has a neural protective effect in brain injury induced by LPS. Key words: Lipid emulsions; Brain injury; Lipopolysaccharide; Toll-like receptors 4; Nuclear factor-κB; Tumor necrosis factor-α; Interleukin-1β; Interleukin-6