Intervention of baicalin/geniposide on vascular endothelial dysfunction caused by PM2.5 exposure and its mechanism based on 5-LOX signaling pathway
Objective To determine the ameliorative effect of baicalin/geniposide(BC/GD)on PM2.5-induced vascular endothelial dysfunction and its mechanism based on 5-LOX/LTB4 signaling pathway.Methods The effect of BC/GD on vascular ring tone in different states was determined with an ex vivo muscle tone tracing technique.Thirty-two rats were randomly divided into a control group,a PM2.5 group,a 30 mg·kg-1 BC/GD group and a 60 mg·kg-1 BC/GD group.The exposure model of PM2.5 was established by tracheal instillation for 2 months,and corresponding drugs were given by gavage for 1 month after the model establishment.After the last administration,HE staining was used to observe the endothelial status of mesenteric artery vasculature.Chemiluminescence detected the level of ROS in the mesenteric arteries;nitrate reductase detected the level of NO;serum levels of inflammatory factors TNF-α,IL-1β,IL-6,TGF-β1,and LTB4 were detected by ELISA;and Western blot detected the levels of 5-LOX,eNOS,and iNOS protein expression.Results BC/GD had no significant effect on the mesenteric artery vascular ring tone in the base state,but it significantly diastoled the vascular ring preconstricted by 5-HT.The nitric oxide synthase inhibitor L-NAME,the cyclooxygenase inhibitor INDO,or L-NAME+INDO all significantly inhibited the vasodilatory effect of BC/GD,and the inhibitory effect of L-NAME was more obvious;PM2.5 at 50 mg·mL-1 and 100 mg·mL-1 reduced the vasodilatory effect of vascular ring on acetylcholine,whereas BC/GD significantly ameliorated the PM2.5-induced attenuation of the diastolic effect.The endothelial integrity of the mesenteric arteries was severely impaired and the endothelium was wrinkled in the PM2.5 group.Compared with those of the control group,the serum levels of TNF-α,IL-1β,IL-6,and LTB4 were higher and the level of TGF-β1 much lower in the PM2.5 group,and the protein expression of 5-LOX and iNOS was significantly increased and the expression of eNOS was decreased in the tissue of mesenteric arteries.The ROS level was elevated and the NO level decreased.Compared with the PM2.5 group,BC/GD improved the degree and integrity of endothelial damage to various degrees,significantly reduced the serum levels of TNF-α,IL-1β,IL-6,and LTB4,and increased the level of TGF-β1.Expression of 5-LOX and iNOS was significantly reduced,and eNOS protein expression elevated in the mesenteric arteries;ROS levels reduced,and NO levels elevated.Conclusion BC/GD can inhibit inflammatory injury by inhibiting the expression of the 5-LOX/LTB4 signaling pathway,down-regulating ROS levels,up-regulating eNOS expression,down-regulating iNOS expression,and increasing the level of NO in the vasculature,and improve the degree and integrity of PM2.5-induced vascular endothelial dysfunction.
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