[Effect of lipoxin A4 on the expression of Toll-like receptor 4 and TNF receptor-associated factor 6 in the liver of obese rats with sepsis].
Cuvinte cheie
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 significantly higher average weight and Lee's index than the normal group (P<0.05). Compared with the normal group, the obesity group had significant 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 significant increases in the serum levels of IL-6 and TNF-α compared with the control subgroup (P<0.05), while the LXA4 subgroup had significant reductions in the two indices compared with the sepsis subgroup (P<0.05). Compared with the normal group, the obesity group had significant 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 significant 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 significant 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.
