| Objective: Coronary heart disease is one of common diseases nowadays which threaten people's health. Atherosclerosis is the basic pathological mechanism of cardiovascular disease and cerebrovascular disease. Since last century, it has attracted many researchers' attention from all over the world. It has been a significant worldwide research issue to explore the mechanism of atherosclerosis, its diagnosis and the therapy scheme. Recent research results reveal that inflammation and immunoreaction plays an important role in the development of atherosclerosis. Heat shock protein 60 (HSP60), as an autoantigen, take part in the processes of autoimmune and inflammation. Probucol is able to reduce blood-fat, and is able to prevent inflammation, oxidization and atherosclerosis. However, it can reduce high-density lipoprotein cholesterol. This limits its clinical applications. Further researches indicate that probucol does not weaken the ability of transferring cholesterol ester, even strengthen this ability. The functional mechanism of probucol in preventing atherosclerosis has been a hot topic in this area. In this study, we established the atherosclerosis rabbit model through high-fat raising and balloon injury. We try to explain the functional mechanism of HSP60 in the development of atherosclerosis and its connection to the stability of plaque, by observing the serum variances in the model, the expression of heat shock protein 60 in the plaque of iliac artery, and the influnence of probucol on the expression of HSP60. This study will provide a new method for the diagnosis of atherosclerosis.Methods: We randomly divided 18 New Zealand rabbits into three groups: control group, high-cholesterol group and probucol group. the control group were raised normal chow. The high-cholesterol group and probucol group were raised with high-cholesterol food (1%cholesterol +5%lard +10%dried egg yolk +84%feed). Four weeks later, the balloon-injured iliac artery angioplasty was performed in the rabbits of the high-cholesterol group and the probucol group, the sham operation was performed in the control group at the same time. After the operation, the high-cholesterol group and probucol group were fed with high-cholesterol food continuely. And we added 1000/mg probucol to each rabbit's daily food in probucol group. After another six weeks, all the rabbits were sacrificed, and the iliac arteries were harvested for morphometrical and immunohistochemical analysis. The area of the atherosclerotic plaque and the area of blood vessels were measured under microscope. The ratio of the area of artery plaque to the area of blood vessels was calculated. The positive expressive area of HSP60 was also measured. During the experimental process, the weights of the rabbits were measured regularly. The serum lipids were measured in the fourth, seventh and the tenth week respectively. Further more, the levels of C-reactive protein, interleukin 6, oxidized low density lipoprotein, maleic dialdehyde, superoxide dismutase and the serum HSP 60 were measured respectively. The statistical software SPSS11.5 was employed to perform comparison and correlation analysis between data in different group.Results:①At the end point of experiment, all these three groups with each group six rabbits were analysed statistically. The weights of these three group of rabbits rise significantly (P<0.05). But there is no statistical difference between these three groups.②In the fourth week, the seventh week and the tenth week, the blood-fat of rabbits in high-cholesterol group and probucol group rise significantly in comparison with control group (P<0.05).③The iliac arteries with balloon-injured and iliac arteries uninjured were HE stained. From these arteries, we can see that the model of atherosclerosis was established successfully. The inner membrane of the artery in control group is smooth and well, and there were no pathological changes. The ratio of the area of plaque to the area of blood vessel in probucol group is lower than high-cholesterol group (P<0.05).④serum IL-6, CRP, ox-LDL, MDA, SOD and HSP60 in control group remain almost the same. However, they are higher in high-cholesterol group and probucol group when it is in the fourth week and tenth week, compared to control group. Serum IL-6,CRP,ox-LDL,MDA and HSP60 are almost the same in probucol group and high-fat group in the fourth weeks, and they become lower in the tenth week in probucol group (PO.05); Further more, SOD keep the same in these two group during the experiment. Serum IL-6,CRP,ox-LDL,MDA and HSP60 are higher in the tenth week than the fourth week in high-fat group and probucol group, and SOD decreased (P<0.05).⑤When the vessels are immunohistochemically processed, there is low level expression of heat shock protein in control group. However, the level of HSP60 is higher in the inner membrane and mid-membrane in high-cholesterol group and probucol group. And the level of HSP60 expression is evidently decreased in probucol group compared to high-cholesterol group.Conclusion:①Probucol can ameliorate the experiment aherosclerosis rabbits' iliac artery. Thus it can prevent the development of atherosclerosis, and this function is independent of the function of reducing the blood fat.②Probucol can reduce the level of serum IL-6,CRP,ox-LDL,MDA. Further more, it has functions of anti-inflammation and anti-oxidizing.③The HSP60 level increases significantly in the atherosclerosis rabbits, which may has a correlation with the instability of the plaque. Probucol can sinificantly decrease the leves of serum and the plaque HSP60, which may be one of the mechanics of probucol's antiatherosclerosis. |
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