The Effects Of Lacidipine On The Expression Of LOX-1 And Neointimal Hyperplasia In Carotid Atherosclerotic Rabbits.

Objective:To observe the effect of Lacidipine on lectin-like oxidized low-density lipoprotein receptor (LOX-1) and neointimal hyperplasia in carotid arteries of hypercholesterolemic rabbit following balloon-injured,and its possible mechanism of antiatheroslerosis.Methods: Thirty healthy balloon-injuried male New Zealand White rabbits were divided randomly and equally into control group: normal animal feeds;Model group:high-fat diet; Laci-L group: high-fat diet and 1mg.kg-1.d-1 Lacidipine ; Laci-H group : high-fat diet and 3mg.kg-1.d-1 Lacidipine ;Atorvas group: high-fat diet and 2.5mg.kg-1.d-1Atorvastatin .The nutrient composition of the fat diet expressed as a percentage of energy was as follows:2% cholesterol,5% lard,0.5% sodium taurocholate and 92.5% normal animal feeds. After 6 weeks,the body weight and femoral blood pressure was measured.Serum triglyceride(TG), cholesterol(TC), low-density lipoprotein-cholesterol(LDL-c), endothelin-1(ET-1), nitric oxide(NO), angiotensinⅡ(AngⅡ)were measured.Left carotid arteries were quickly obtained and stored on liquid nitrogen for subsequent analysis. A little part of carotid arteries were fixed,embedded and bladed for hematoxylin/eosin (HE) staining. Image analysis system was applied to measured the area of intimal and neointimal (SI),the area of media(SM), and the ratio of SI /SM was obtained. The expression of LOX-1mRNA in carotid artery were evaluated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), LOX-1protein expression was examined by immunohistochemistry。Results: (1)The typical caroid atherosclerostic plaques were observed in all fat diet groups.Compared with model group, Laci-L,Laci-H and Atorv significantly reversed the progression of caroid plaques.(2)Comparing to model, Laci-H can step down systolic blood pressure(p<0.05). (3) The level of serum TC,TG and LDL-C increased significantly in model group(p<0.01).Lipid profile was no difference between model and Laci-L or Laci-H group(p>0.05). (4) Compared to control group, the level of serum ET-1 angiotensinⅡ(AngⅡ)in model group increased (P<0.01),the level of serum NO decreased(P<0.01)。Compared to model group, ET-1 in Laci-L group decreased (P<0.05), Laci-H group (P<0.01); AngⅡin Laci-L and Laci-H group decreased(P<0.05);NO in Laci-H group increased(P<0.05). (5) On the injured side, SI /SM ratio of carotid artery in model group was much thicker than that in control group. No significant difference was found in SI /SM ratio of carotid artery among Laci-L,Laci-H and control group (P>0.05).(6) The expression of LOX-1 mRNA and protein were much more in model group than that in control group(p<0.01). Compared to model group, LOX-1 expression level drops in Laci-L,Laci-H group(p<0.01).Conclusion: (1)Lacidipine can inhibit carotid artery intimal proliferation, delayed a significant progression of arterial lesions of AS in rabbits.(2) Lacidipine can decreased the level of serum ET-1 and AngⅡ,increased NO.(3) Lacidipine at a dosage of 1mg.kg-1.d-1 and 3 mg.kg-1.d-1 markedly decreased the LOX-1 expression level in endothelium and neointima. Antiatherosclerosis of Lacidipine maybe relate to inhibition of expression of LOX-1 in endothelium.