The Effect Of Probucol Combined With Rosuvastatin On Expression Of LOX-1in Aorta Of Apo-E Gene Knockout Mice

Obejective:Atherosclerosis is a complicated physiological process, Severval studies demonstrated that oxidized low density lipoprotein(ox-LDL) plays a crucial role in the hypertension diabetes and atherosclerosis. Lectin-like oxidized low density lipoprotein receptor-1(LOX-l) is the main ox-LDL receptor of endothelial cells, contributes to the atherosclerotic plaque formation and progression by several mechanisms,including the induction of endothelial cell activation and dysfunction, macrophage foam cell formation,and smooth cellular migration and proliferation. Recently LOX-1calls more attention and is realized as a targets of atherosclerosis treatment.this study applied Apo-E-/-mice to build models of atherosclerosis, elucidate affection of rosuvastatin and probucol on the accumulation of lipoproteins on plaque and the expression of LOX-1in aorta,to explain the mechanism of inhibitory effect on atherosclerosis.Methods:1.Molding:32male Apo-E gene knockout male mice aged8weeks old were randomly divided into4groups:control group which fed with high-fat diet; probucol group which fed with high-fat diet contained1%probucol; rosuvastain group, treated with high-fat diet and gave rosuvastain by swallow; the united group,beside treaded with hight-fat diet which contain1%probucol,gave rosuvastatin by swallow. They are made the models of atherosclerosis after fed continuously12weeks in the SPF animal laboratory.Every week these mice were weighed and recorded down the changes of the mice body weights.2.Materials:Aninals were anatomized under an operation microscope after12weeks to observe lipid deposition on aorta and atherosclerotic plaque volume.3.Take out the aorta and its main branches,use enzyme-linked immuno sorbent assay(ELISA) to qualify content1of these Apo-E-/-mice.Results:1.The weight of all animals were significantly increased at the end of the experient than before(p<0.05).Treatment group weight is significantly less than the control guoup, the difference have statistics significant when treating after8weeks. At12weeks, the control group, probucol group, rosuvastatin group and united group mice weights respectively is:(31.18±1.72)g,(30.81±0.91) g,(28.91±1.09) g,(27.63±0.93)g. There is significant difference between drug treatment groups and control group (p<0.01).2.Compared with control group, there is remarkable difference lipid deposition and atherosclerosis plaque volume significantly under microscope in treatment groups, especially in united group.3.At12weeks, the control group, probucol group, rosuvastain group and united group mice, the content of in aorta, respectively is:1.0296±0.15122,0.7240±0.13367,0.4902±0.03934,0.4156±0.07541.There is significant difference between the drug treatment groups and control(P<0.01).Among drug treatment groups, there is significantly different between probucol group and other two groups, but no significant difference between rosuvastain group and united group mice.4.The weights of mice are positive related with the content of LOX-1in aorta.(r=0.652,p<0.01)Conclusion:1.Probucol, rosuvastatin and their combination can slow down the growth of mice weight,in spite of treating with high-fat diet.2.probucol,rosuvastain,and their combination can significantly decreased atherosclerotic lesion area in the aorta.3.Both probucol and rosuvastatin alone or their combination could reduce the content of LOX-1in aorta, which can indicate the mechanism of Anti-atherosclerosis,4.The weights of mice are positive related with the content of LOX-1in aorta. Probucol and rosuvastatin could inhibit the weight increasing so down-regulate the expression of LOX-1in aorta.