Effect Of Rennin Inhibitor, Aliskiren, On Atherosclerotic Plaque And Inflammation In Rabbits

[Objective]:To explore the effects of rennin inhibitor, aliskiren, on atherosclerosis and Inflammatory response in atherosclerotic plaque.[Methods]:Rabbit atherosclerotic model was established by high fat diet,and24New Zealand rabbits were randomly divided into single high fat group(n=8), aliskiren group(n=8) and normal control group(n=8). Rabbits in high fat group were fed with high fat diet(1.5%cholesterol and5%lard oil), those in aliskiren group were fed with high fat die and aliskiren (25mg-kg-1·d-1),and those in normal control group were fed with regular diets.Rabbits were fed for16weeks,and were sacrificed, Thoracic aorta samples were obtained for histological examination and immunohistochemistry was used to detect the expression of biomarkers of macrophage(RAM11)and lectin like oxidized LDL receptor-1(LOX-1) in plaque,which were indicated as ratios of area of positive expression.[Results]:1. The comparison of serum lipid levels among the three groups:After four months, the concentration of serum TC and LDL-C in the high fat group and the aliskiren group have no statistical significance (P>0.05),but they were significant higher than that in the normal control group (P<0.01, P<0.01).2. The influence of morphology in plaques:The high fat group and the aliskiren group both have atherosclerotic plaque formation.The high fat group has obvious, multiple, discontinuous plaque formation, the aliskiren group has less smaller plaque formation than high fat group.The normal control group has complete, smooth hemal wall and it has no plaque formation. 3. The extent of atherosclerosis compared of each group:The intimal thickness, intimal/media thickness ratio, intimal area and intimal/media area ratio were markedly lower in aliskiren group than that in in high fat group(P<0.01),but they were significant higher than that in normal control group (P<0.001).4. The influence of lipid in plaques:Oil Red staining showed that the high fat group’s plaques contain more lipid components than that in aliskiren group, the average area ratio of lipid components were (34.38+2.07)%,(47.12+4.16)%,respectively,with significant differences between the two groups(P<0.01).5. The changes of Macrophages expression in plaques:The immunohistochemical staining results showed that the high fat group have a large number of macrophage exist and distributed intensively, the aliskiren group’s macrophage distributed Sparsely, the average area ratio of macrophage positive staining signal were (30.63+2.26)%,(21.13+2.10)%, respectively,with statistical differences between them(P<0.01),6. The changes of LOX-1expression in plaques:The immunohistochemical staining results showed that the high fat group and the aliskiren group both have LOX-1positive expression.The statistical analysis showed that the expression level of LOX-1in aliskiren group(11.38+1.69)%Obviously less than that in high fat group (16.75+1.67)%,there is statistical differences between them(P<0.05).[Conclusion]:Rennin inhibitor, Aliskiren, played a role in anti-atherosclerosis. The mechanism connection with reduced intimal LOX-1protein expression and the macrophages infiltration, inhibits the inflammatory process of the atherosclerosis.