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

Objective:Recently Lectin-like oxidized low density lipoprotein receptor1(LOX-1), calls more attention and is realized as a targets of atherosclerosis treatment. So far, still no drugs have the definite function to intervene the LOX-1expression, so delay the AS process, thereby reducing the occurrence of acute cardiovascular events related to coronary heart disease (CHD). 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.Try to explain the mechanism of inhibitory effect on atherosclerosis.Methods:Thirty-two Apo-E gene knockout male mice, eight-weeks old, were randomly divided into four groups:control group, which treated with high-fat diet and intragastric gavage; probucol group which treated with high-fat diet but containing1%probucol and intragastric gavage; rosuvastatin group, treated with high-fat diet and gave rosuvastatin by gavage; the united group,beside treaded with hight-fat diet which contain1%probucol,gave rosuvastatin by gavage. Every week these mice were weighed and recorded down the changes of the mice body weights, After twelve weeks, mice were anatomized in the view of microscope, meantime to observe lipid deposition on aorta and atherosclerotic plaque volume. And then take out the aorta and its main branches. Use ABI7900HI Real-time PCR machine to quantify relatively expression level of these mice LOX-1mRNA.Results:1. The weight of treatment groups of experimental mice show slow pace than the control group, then 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. Under Microscope, there is remarkable difference lipid deposition and atherosclerosis plaque volume significantly, comparing with control group with drug treatment group. 3. The control group, probucol group, rosuvastatin group and unite group mice,the relative expression of LOX1mRNA in aorta, respectively is:1.53±0.35,0.54±0.51,0.32±0.25,0.25±0.23. There is significant difference between The drug treatment groups and control group (p<0.05).And there is no difference among tree drug treatment group.4. The weights of mice are positive related with the expression of LOX-1mRNA in aorta.(r=0.698,p<0.001)Conclusion:1. Probucol, rosuvastatin and their combination can slow down the growth of mice weight,in spite of treating with high-fat diet.2. Administration of probucol alone and rosuvastatin alone significantly decreased atherosclerotic lesion area in the aorta,if combined there was excellent effect.3. Both probucol and rosuvastatin alone or their combination could down-regulate the expression of LOX-1mRNA in aorta, it can indicate the mechanism of Anti-atherosclerosis.4. The weights of mice are positive related with the expression of LOX-1mRNA in aorta. Probucol and rosuvastatin could inhibit the weight increasing so down-regulate the expression of LOX-1mRNA in aorta.