Effects Of Retinoic Acid On Lipopolysaccharide-induced Vascular Inflammation And Oxidative Stress Through The TLR4/NF-κB Pathway

ObjectiveThis study aimed to study potential protective effects of retinoic acid(RA)on lipopolysaccharide(LPS)-induced vascular inflammation and oxidative stress and to explore its possible molecular mechanism.MethodsSD rats were given RA and TLR4 inhibitors for 2 weeks after continuous oral gavage,except for the control group,the LPS group,the RA 3 mg/kg group,the RA 15 mg/kg group,and the TLR4 inhibitor group(TAK-242,3 mg/kg)were intraperitoneally injected with LPS(10 mg/kg)to establish a model of vascular inflammation.The tension was measured by DMT system;the content of nitric oxide(NO)in rat serum was determined by nitrate reductase method;the levels of IL-18,IL-1β,TNF-α,IL-6 and GSH-px in serum were detected by ELISA;the activity of superoxide dismutase(SOD)and malondialdehyde(MDA)in serum were detected by WST-1 and TBA methods,respectively;the level of vascular reactive oxygen species(ROS)was detected by DHE fluorescent probe;the expression of NF-κB p65 was detected by immunohistochemistry;the expressions of TLR4,eNOS and p-eNOS were detected by western blotting.ResultsCompared with the control group,after administration of lipopolysaccharide,(1)p-eNOS and NO(p <0.01)decreased;(2)serum IL-18,IL-1β,TNF-α and IL-6(p <0.01)increased(3)MDA and ROS(p <0.01)increased in serum;(4)SOD and GSH-px(p <0.01)decreased in serum;(5)TLR4 and NF-κB p65(p <0.01)protein expression increased in blood vessels.Compared with the LPS group,(1)p-eNOS and NO(p <0.01)increased after RA;(2)serum levels of IL-18,IL-1β,TNF-α,and IL-6(p <0.01)decreased;(3)MDA and ROS(p <0.01)decreased in serum;(4)SOD and GSH-px(p <0.01)increased in serum;(5)TLR4 and NF-κB p65(p <0.01)protein expression decreased.Compared with the LPS group,after administration of TLR4 inhibitors,(1)p-eNOS and NO(p <0.01)increased;(2)serum levels of IL-18,IL-1β,TNF-α and IL-6(p <0.01)Decreased;(3)MDA and ROS(p <0.01)in serum decreased;(4)SOD and GSH-px(p <0.01)increased in serum;(5)TLR4 and NF-κB p65(p <0.01)protein expression decreased.ConclusionThe results show that RA can inhibit LPS-induced vascular inflammation and oxidative stress,which may play a role through the TLR4 / NF-κB p65 signaling pathway.These findings provide a theoretical basis for the further study of RA in the treatment of LPS-induced vascular inflammation and oxidative stress.