Objective To study potential protective effects of retinoic acid (RA) on lipopolysaccharide (LPS)-induced vascular inflammation and oxidative stress and explore its possible molecular mechanism. Methods After SD rats were given RA and TLR4 inhibitors by oral gavage for 2 weeks, except for the control group, LPS group, RA 3 mg/kg group, RA 15 mg/kg group and TLR4 inhibitor group (TAK-242, 3 mg/kg), LPS (10 mg/kg) was injected intraperitoneally to establish a vascular inflammation model. Vascular tension measurement system was used to detect vasodilation function, nitrate reductase method was used to detect nitric oxide (NO) content in rat serum. Serum IL-18, IL-1β, TNF-α, IL-6 and GSH- px level was detected by ELISA method, WST-1 and TBA methods were used to detect the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) in the serum respectively, DHE fluorescent probe was used to detect the level of vascular reactive oxygen species (ROS), and immunohistochemical method to detect the expression of vascular NF-κB p65, Western blotting to detect the expression of vascular TLR4, eNOS and p-eNOS. Results Compared with the LPS group, RA can improve the vasodilation function, increase the levels of p-eNOS and NO, decrease the serum inflammatory factors IL-18, IL-1β, TNF-α, IL-6 level, and reduce the serum MDA and ROS, increase the production of SOD and the release of GSH-px in the serum, and down-regulate the expression levels of vascular TLR4 and NF-κB p65. In addition, the effect of RA on LPS-induced vascular inflammation and oxidative stress was similar to that of TLR4 inhibitors. Conclusions RA has an inhibitory effect on LPS-induced vascular inflammation and oxidative stress, through the TLR4/NF-κB p65 signaling pathway.
Key words
Retinoic acid; /
/
TLR4/NF-κB; /
Vascular endothelial dysfunction; /
Inflammation; /
Oxidative stress
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