Effect Of Oleoylethanolamine On Treg/Th17 During Atherosclerotic Plaque Formation And The Related Mechanism

Background:Atherosclerosis is one of the most common vascular diseases in the world that seriously damage human health.The mechanism of the disease is that a large amount of lipids accumulate in the intima of the blood vessels,forming atherosclerotic plaques.Late plaque may rupture to form a thrombus,clogging the lumen of the blood vessel.A large number of studies have shown that the formation,development and complications of AS are closely related to the intravascular immune inflammatory response.Oleoylethanolamine is an endogenous fatty acid ethanolamine compound found in tissues and circulating blood.Studies have shown that OEA has many biological effects such as reducing lipid metabolism,neuroprotection and prolonging life span.Previous studies in our laboratory have confirmed that OEA can improve the deterioration of AS,but the role of Treg/Th17 cell balance in this process remains unknown.Objective:The effect of OEA on Treg/Th17 during the pathological process of atherosclerosis and its mechanism.Research Methods:1)In vivo experiments:ApoE-/-(male)mice were fed with high fat diet,and OEA group was treated intraperitoneally daily.The size and number of plaques and unstable plaques in aorta were observed after 20 weeks.The expression of Treg/Thl7 cells in aortic plaque,blood and spleen was observed by immunohistochemistry and Flow Cytometry.Expression of proteins such as Foxp3,TGF-?,IL-17,IL-6,AMPK,p-AMPK,and PPAR? were detected by Western Blot.2)In vitro experiments:ox-LDL induced the differentiation of primary spleen cells into Treg/Th17 cells under OEA pre-protection;use Flow Cytometry and western blot to investigate the effect of OEA on Treg/Thl7 cells in spleen cells;extract spleen cells from PPARa-/-Mouse,and explore the role of OEA and PPARa by using flow cytometry and Western Blot;use si AMPK to explore the role of OEA and its relationship with AMPK.Experimental Results:1)In vivo experiments:In vivo experiments:OEA can significantly reduce the formation of AS plaques,regulating the balance of Treg/Th17 in plaque,blood and spleen,down-regulate the expression of inflammatory factors such as IL-17 and IL-6,and up-regulate the inhibitory factors such as TGF?.During the process,OEA activates PPARa and AMPK targets.2)In vitro experiments:OEA significantly reduced the inflammatory response induced by ox-LDL,OEA induces Naive T cells into Treg cells,the kind of action reversed with PPARa-/-mice,and after si AMPK for Treg/Th17 role has also been reversed,indicating that OEA may be related to Treg/Th17 role and PPARa and AMPK.Conclusion:OEA can significantly improce the pathological process of AS and reduce the formation of plaque.It promotes the differentiation of Naive T cells into Treg cells,maintains the balance of Treg/Th17 in plaque,blood and spleen,and regulates the secretion of pro-inflammatory and anti-inflammatory factors.These functions of OEA may be realized by activating PPARa and AMPK targets to regulate the balance of Treg/Th17 cells before finally achieve anti-AS effects.