Effect of lipoxin A4 on the expression of Toll-like receptor 4 and TNF receptorassociated factor 6 in the liver of obese rats with sepsis

Abstract:

Objective To study the protective effect of lipoxin A4 (LXA4) against sepsis induced by lipopolysaccharide (LPS) in rats with obesity and its effect on the expression of Toll-like receptor 4 (TLR4) and TNF receptor-associated factor 6 (TRAF6) in the liver.Methods A total of 60 male Sprague-Dawley rats aged three weeks were randomly divided into a normal group and an obesity group, with 30 rats in each group. A rat model of obesity was established by high-fat diet. Each of the two groups was further randomly divided into control group, sepsis group, and LXA4 group, and 8 rats were selected from each group. The rats in the control, sepsis, and LXA4 groups were treated with intraperitoneal injection of normal saline, LPS, and LXA4+LPS respectively. Twelve hours later, blood samples were collected from the heart and liver tissue samples were also collected. ELISA was used to measure the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Western blot was used to measure the protein expression of TLR4 and TRAF6 in liver tissue. Quantitative real-time PCR was used to measure the mRNA expression of TLR4 and TRAF6.Results After being fed with high-fat diet for 6 weeks, the obesity group had signifcantly higher average weight and Lee's index than the normal group (P < 0.05). Compared with the normal group, the obesity group had signifcant increases in the serum levels of IL-6 and TNF-α (P < 0.05). In the normal group or the obesity group, the sepsis subgroup had signifcant increases in the serum levels of IL-6 and TNF-α compared with the control subgroup (P < 0.05), while the LXA4 subgroup had signifcant reductions in the two indices compared with the sepsis subgroup (P < 0.05). Compared with the normal group, the obesity group had signifcant increases in the protein and mRNA expression of TLR4 and TRAF6 (P < 0.05). In the normal group or the obesity group, the sepsis subgroup had signifcant increases in the protein and mRNA expression of TLR4 and TRAF6 compared with the control subgroup (P < 0.05). Compared with the sepsis subgroup, the LXA4 subgroup had signifcant reductions in the protein and mRNA expression of TLR4 and TRAF6 (P < 0.05).Conclusions LXA4 can reduce the serum levels of IL-6 and TNF-α and alleviate inflammatory response. LXA4 can inhibit the expression of TLR4 and TRAF6 in the liver of septic rats, possibly by inhibiting the TLR4 signaling pathway.