Atherosclerotic Plaque Of Myeloperoxidase And P53 Protein Expression In The Experimental Research

Atherosclerosis is the common disease which is harmful to people’s health,and it is the leading cause of death of cardiovascular and cerebrovascular diseases. With the continuous improvement and development of CT and MR angiography, it is possible for non-invasive imaging diagnosis of atherosclerotic plaques,and the existence and morphological characteristics of atherosclerotic plaque continue to be clear detection and description, greatly improving the prevention and treatment of cardiovascular and cerebrovascular diseases.However, the present question is:how to accurately predict the risk of cardiovascular and cerebrovascular events in atherosclerosis patients? Through the establishment of atherosclerosis animal models,carrying out the study of imaging and pathology of atherosclerotic plaque is an important research of prevention and control of cardiovascular and cerebrovascular disease, and is the key to promote the prevention and treatment of cardiovascular and cerebrovascular diseases. This study intends to establish atherosclerotic animal model through vascular endothelial injury,and to explore the feasibility of3.0TMR imaging detection of rabbit artery atherosclerotic plaques, and the pathology detection of expression of MPO and P53protein in atherosclerotic plaques,to lay an experimental foundation for the further development of molecular imaging. This study include three parts.Part Ⅰ:The establishment of animal model of rabbit carotid artery atherosclerosis. Part Ⅱ:MR imaging evaluation of carotid artery atherosclerosis in rabbit model. Part Ⅲ:The expression of myeloperoxidase and P53protein in carotid atherosclerotic plaques in rabbit model.Part Ⅰ:The establishment of animal model of rabbit carotid atherosclerosisObjective To establish model of rabbit carotid atherosclerosis based on the endothelial injury.Materials and Methods30male New Zealand white rabbit were randomly divided into4weeks group (n=8),8weeks group (n=10),12weeks group (n=12). All New Zealand white rabbits underwent right femoral artery puncture, injury right carotid artery by expansing balloon under DSA, then feed them with high fat diet (containing2%cholesterol).8,10,12rabbits were executed respectively at4weeks,8weeks,12weeks after surgery.Then take out the right carotid artery, making paraffin section and HE staining.Observe the changes of artery wall, vascular intima and lumen of right carotid artery.Results The pathological findings of vascular intimal at4weeks:vascular smooth muscle slight thickening with inflammatory cells infiltration, the lumen is not significantly narrow. The pathological findings of vascular intimal at8weeks:vascular intima thickening obviously with massive inflammatory cells infiltration, the smooth muscle cells in tunica is of marked hyperplasia, the lumen is narrow. The pathological findings of vascular intimal at12weeks: vascular wall thickening obviously with the formation of atherosclerotic lipid plaque and infiltration of massive foam cells and inflammatory cells, the local boundary of intima and tunica is not very clear,the intima is obviously narrow.Conclusion The application of vascular endothelial injury and high fat diet can successfully establish model of rabbit carotid atherosclerosis. It provides experiment basis for the further research of atherosclerosis.Part Ⅱ:MR imaging evaluation of carotid artery atherosclerosis in rabbit modelObjective To observe MRI findings in the process of atherosclerotic lesions and the comparison of MR findings and pathology.Materials and Methods30male New Zealand white rabbits were randomly divided into4weeks group (n=8),8weeks group (n=10),12weeks group (n=12), injury right carotid artery by expansing balloon under DSA, then feed them with high fat diet (containing2%cholesterol) after injury.8,10,12rabbits were executed respectively at4weeks,8weeks,12weeks after surgery, all rabbits underwent neck MR scanning before execution. Then take out right carotid artery, making paraffin section and HE staining. Use Neusoft PACS/RIS system and motic pathology digital camera systems to measure thickness of right carotid artery wall. Use Peason’s correlation test in SPSS10.0software to analysis the results of the two results.Results The MR findings of vascular intimal at4weeks:artery wall shows slight hyperintensity with thickening, the lumen stenosis is not significant. TOF shows right carotid artery is not abnormal.The pathology shows vascular smooth muscle slight thickening with inflammatory cells infiltration, the lumen is not significantly narrow. The MR findings of vascular intimal at8weeks:arterial wall thickening with enhanced signal in T1W and T2W, the lumen is narrow, TOF shows local arterial wall is coarse, the lumen stenosis irregularly, the pathology shows vascular intima thickening obviously with massive inflammatory cells infiltration, the smooth muscle cells in tunica is of marked hyperplasia, the lumen is narrow. The MR findings of vascular intimal at12weeks:arterial wall annular thickening obviously, the signals of arterial wall is isointensity in T1W an slightly hyperintensity in T2W, TOF shows local arterial wall is coarse, the lumen stenosis irregularly, the pathology shows vascular wall thickening obviously, atherosclerotic lipid plaque formation in artery wall, and massive foam cells and inflammatory cells in plaque, the local boundary of intima and tunica is not very clear,the intima is obviously narrow.The average thickness at carotid atherosclerotic plaque in12weeks group measured by PACS/RIS system and motic digital camera system are566±51μm、564±48μm. There is correlativity in carotid artery thickness of the two results,the correlation coefficient is0.926.Conclusion MR can detect the formation of atherosclerotic lesions, and shows the change of the artery wall and lumen. MR findings reflects the pathology change of atherosclerotic lesions to a certain extent.Part III:The expression of myeloperoxidase and P53protein in atherosclerotic plaques in rabbit modelObjective To observe expression and distribution of myeloperoxidase and P53protein in atherosclerosis plaques.Materials and Methods30male New Zealand white rabbits were randomly divided into4weeks group (n=8),8weeks group (n=10),12weeks group (n=12), then injury right carotid artery with expansing balloon,feed them with the high fat (containing2%cholesterol) after injury.8,10,12rabbits were executed respectively at4weeks,8weeks,12weeks after surgery. Select12cases specimens in which atherosclerotic plaque is formed, detect the expression and distribution of myeloperoxidase and P53protein with immunohistochemistry methods.Results MPO and mutant P53protein were expressed positively in atherosclerotic plaque.The positive expression rate of MPO and mutant P53protein in rabbit carotid atherosclerotic plaque of12cases are90.9%、89.7%,the statistical test between them has no significant difference (P>0.05). MPO was distributed diffusely in atherosclerotic plaque, mutant P53protein mainly was distributed in the subintima of the atherosclerotic plaque. MPO and mutant P53protein were expressed positively in cell membranes and cell plasma, shows ribbon, rings, patchy tan or brown shading area, while MPO and mutant P53protein were expressed negatively in nuclei.Conclusion The expression of MPO and P53gene mutations plays an important role in the formation of rabbit atherosclerotic plaque.