The Study Of The Relationship Between CEUS,MMP-2,RAM-11 And The Neovascularization In Rabbit Carotid Atherosclerotic Plaque

Objectives: The purpose of this study is establishing the rabbit carotid atherosclerotic model and observing the value of contrast-enhanced ultrasound (CEUS) in the detection of neovascularization development. At the same time we detected the expression tendency of MMP-2,RAM-11 and CD31 by using the immunohistochemical method and found out the correlations between them. Thus we hope to further elucidate the mechanism and pathological process of the carotid atherosclerotic plaque, search the clinical treatment and provide a theoretical insight of seaching for effective drugs.Methods: Forty of the male New Zealand white rabbits were randomly divided into 4 groups: Group A (the blank control group),group B (hypsocholesterol diet group),group C (silicone collar intervention and hypsocholesterol diet for 14 days group),group D (silicone collar intervention and hypsocholesterol diet for 28 days group). Ultrasonography and CEUS were carried out for the purpose of understanding the situation of the carotid atherosclerosis plaque and the neovascularization at the time points of the beginning of the 14th dayand the 28th day, by the application of the mapping of the time-intensity curve (TIC) to record the peak intensity (PI). Pathologic changes were evaluated by the way of immunohistochemistry with hematoxylin and eosin stain. The expressions of MMP-2, RAM-11 and CD31 were detected by immunohistochemistry. Finaly, the correlations between the mean optical density (MOD) of the positive cells and indexes of neovascularization were analyed between each group.Results: The rabbit carotid atherosclerotic model was successfully established by using silicone collar intervention and hypsocholesterol diet. On the 14th and 28th day, the plaques and neovascularization in the model groups were detected. The lipid results showed that the lipids of hypsocholesterol diet group were higher than that of common diet group (P<0.05). In the model group, HE staining showed there were plaques forming, endometrial thickening and local smooth muscle cells disorder proliferation and migration. Immunohistochemistry showed there were positive MMP-2, RAM-11 and CD31 expressions in the plaques. There was a significant difference of the MOD between group C and D (P<0.05). Correlative analysis showed positive correlations between the expressions of MMP-2,RAM-11 and neovascularization (P<0.01).Conclusions:1. The rabbit carotid atherosclerotic model can be successfully induced by silicone collar intervention and hypsocholesterol diet.2. Contrast-enhanced Ultrasound can detect dynamic changes of the neovascularizations in the rabbit carotid atherosclerotic plaques.3. There were neovascularizations in the atherosclerotic plaque. and the quantity of the neovascularizations has positive correlection with the positive expressions of MMP-2and RAM-11.