Hyperuricemia And Lipid Metabolism Disorders And The Expression Of Lox-1 And PCSK-9/NARC-1 In The Aorta And Liver Of Hyperuricemia Rats

Objective : Observe level changes of lipids 、 ox-LDL and PCSK-9 induced by hyperuricemia in rats,observe the possible pathological changes of aorta and liver in hyperuricemia rats,observe the influence of hyperuricemia on expression of Lox–1、PCSK-9/NARC-1 in aortic endothelial cells and liver cells of hyperuricemia rats,in order to investigate the role of hyperuricemia in the development of atherosclerosis and its possible mechanism.Methods:18 healthy male Wistar rats were randomly divided into hyperuricemia group(HUA group,10rats)and normal control group(NC group,8rats).High feed yeast,adenine solution to fill the stomach,subcutaneous injection of oxygen oxazine acid potassium solution were used to establish durative hyperuricemia rats model.The levels of serum uric acid(UA),triglyceride(TG),total cholesterol(TC)and low-density lipoprotein cholesterol(LDL)in angular vein blood of both groups were measured every four weeks.The levels of proprotein convertase subtilisin/kexin type9(PCSK-9)and oxidized lowdensity lipoprotein(ox-LDL)in angular vein blood of both groups were measured at the begin and the end of the experiment.At the end of the experiment,the possible pathological changes of aorta and liver were observed by the method of HE stain,gormori methenamine silver staining method was used to observe uric acid salt deposition in aortic wall,and the expression of Lox–1 and PCSK-9/NARC-1 in aorta and liver cells was evaluated by the method of immunohistochemical analysis.Results:By end of the 16 th week,the levels of serum UA,TG,TC,LDL,ox-LDL and PCSK-9 were higher in HUA group than in NC group,the differences were statistically significant(P<0.01).The rats in HUA group show aortic endothelial cells damage、increase of aortic intima-media thickness、calcium salt deposition in aorta,whereas rats in NC group are totally normal,but typical change of atherosclerosis is not found in aorta of HUA group rats.None rat of the two groups show urate deposition in aortic wall.The expression of Lox–1 and PCSK-9/NARC-1 in liver cells of hyperuricemia rats is significantly higher than the rats of NC group(P<0.01),and the expression of Lox–1 and PCSK-9/NARC-1 in aortic endothelial cells and smooth muscle cells of hyperuricemia rats are higher than the rats of NC group(P<0.05)Conclusions:1.Higher levels of TG、TC、LDL and ox-LDL can be caused by durative hyperuricemia in rats,higher level of LDL may be caused by higher level of PCSK-9.2.Early change of atherosclerosis as aortic endothelial cells damage、increase of aortic intima-media thickness can be induced by hyperuricemia in rats,but typical change of atherosclerosis is not found.Durative hyperuricemia may not cause atherosclerosis directly by urate deposition in aortic wall,but may cause calcium salt deposition leading to hardening of the aorta.3.Increased expression of Lox-1 in hyperuricemia rats suggest that hyperuricemia may involve in the process of oxidative stress and inflammatory reaction,and increased expression of Lox-1 in aortic endothelial cells and smooth muscle cells may be one of the possible mechanisms of hyperuricemia involved in atherosclerosis.4.Increased expression of PCSK-9/NARC-1 in liver cells of hyperuricemia rats may cause higher levels of serum PCSK-9 and LDL,increased expression of PCSK-9/NARC-1 in aortic endothelial cells and smooth muscle cells may be the early change of atherosclerosis caused by hyperuricemia.