P-selectin Expression In Atherosclerotic Rabbits Models And The Effect Of Melatonin On It’s Exression

Objective Atherosclerosis is one of the most widespread conditions that alwaysthreaten human health and survival. The formation and development of atherosclerosisis always a chronic process. Its precise etiopathogenisis is not clear till now. It isdemonstrated that P-selectin plays a vital role in it. P-selectin which is also calledcluster of differentiation62P(CD62P) belongs to the family of adhesion molecule.It is amarker of platelet activation.Firstly,it is found on activated platelets, recent studiesshow it is also found on activated endothlial cells and atheromatous plaques.P-selectinfacilitates the formation and advancement of atherosclerosis by promoting theadhension of white blood cells and thrombogenesis. Melatonin is a hormone secretariedby pineal gland. In recently years, the investigations have verified that melatonin havemany functions in atherosclerosis formation, the main mechanism is antioxidation. Wedo not know whether it can inhibit the expression of P-selectin in the formation ofatherosclerosis. There are few reports in and out of abroad. In view of this, our studyestablished the atherosclerotic rabbits models, detected the expression of P-selectin inthis model, and investigated the effect of melatonin on the expression of atheroscleroticplaques and platelet P-selectin.Methods27rabbits were randomly divided into3groups: control group(Group Z),high-fat diet induced atherosclerosis group(Group H) and melatonin group(GroupM).Group Z received basal diet,Group H and Group M received high-fat diet. Fourweeks later, Group M received melatonin(5mg/kg/day). At the end of12weeks, allrabbits were sacrificed. Disease markers, including lipids, P-selectin, were assayedusing flow cytometry, innunohistochemistry. Results The atherosclerosis model was established successfully after being fed withhigh fat for12weeks, the serum cholesterol (TCH), triglyceride(TG), low-densitylipoprotein(HDL) and high-density lipoprotein(LDL) increased obviously, and isstatistically different compared with the normal control group(P<0.05). In group M, thelevel of the serum TG, TCH and LDL degraded when compared with group H(P<0.05),while HDL increased. This indicated that melatonin may decrease serum TCH, TG andLDL, but increase HDL. HE staining assay shows the vascular intima of model groupthickened, with a lot of foam cells gathering underneath. While foam cells of thetreatment group significantly reduced. Meanwhile, after the treatment of melatonin for12weeks, the expression of P-selectin decreased compared with that of high-fat dietgroup. Rabbits fed with high-fat diet showed more plaque area and P-selectinexpression both in the plaque and platelet surface. After the treatment of melatonin,there was a significant decrease in serum lipids and the formation of the plaque by flowcytometry, innunohistochemistry. Melatonin also inhibited the expression of P-selectinboth on the plaque and platelet surface.Conclusions Melatonin may recover the disbalance among serum lipids during theprogression of atherosclerosis, the expression of P-selectin was increased inatherosclerosis model. It can be served as a risk factor and marker of atherosclerosis,and also plays a crucial role in the formation and progression in atherosclerosis.Fothermor, melatonin could down-regulate P-selectin expression both on atheroscleroticplaques and on the surface of platelet.