| ObjectionAtherosclerosis is one of the main pathongeny diseases that threaten the health of human being, it' s pathogenesis dosen' t yet clarify completely. Now it is accepted that a series inflammatory responses occure on the basis of vascular endothelial cell injured. Recently some studies showed that calcium antagonists can protect the function of endothelial cell. Lercanidipine is a new dihydropyri-dine calcium antagonist, which pocesses definitely the effect of antihypertentive function , there is report in abroad that it still has the antiatherosclerotic activities , but now such kind of report was not yet seen in domestic. This experiment replicated the atherosclerotic model of cholesterol-fed rabbits, effects of different does of lercanidipine on vascular endothelium functions and vascular cell adhesion-1 expression in atherosclerotic rabbits were observed, and the antiatherosclerotic effects of the new dihydropyridine calcium antagonist lercanidipine were evaluated.Methods1. Animal model and groupJapan white rabbits ( n = 32 ) (1.5-2.5 kg ;4-5months ) were randomly divided into four groups: (1) normal control group ( n = 8 ) ; normal diet; ( 2 ) high-lipid control group(n = 8) : cholesterol-rich diet; (3) low dose lercanidipine-treated group (n = 8) : cholesterol-rich diet + lercanidipine 1mg kg-1 day-1; (4) high dose lercanidipine-treated group ( n = 8 ) : cholesterol-rich diet + lercanidipine 10mg kg -1May-1. After 12 week all animals were killed.2. Sample collecting and detecting(1) Determination of blood biochemical parameters: The blood sample were collected separately from the ear peripheral vein of rabbits before and after 4,8, 12 week of experiment. Separated serum or plasma and kept in -70C deep low temperature refrigerators, unified to detect the values of the serum lipid,ET and NO.( 2 ) pathologic specimen: Selected the aorta 5 nnn close to the aorta bow , used for the pathologic and morphologic observation and immunohistochemical a-nalysis.3. Statistic analysisAll data are expressed as means s. d. All statistical calculations were performed by SPSS11.0 software. Statistical comparison of all numerical data between groups were performed by one-way ANOVA. A P value < 0.05 was taken as statistically significant.Result1. Change of serum lipidValues of serum lipid did not show any significant difference among the group before experiment. Serum total cholesterol and low density lipoprotein cholesterol values of high-lipid control group, low dose lercanidipine-treated group and high dose lercanidipine-treated group increased significantly compared with those of normal control group (P <0.01) ,and there is no difference among the three groups ( P > 0. 05 ). The level of high density lipoprotein cholesterol and triglyceride of each group did not show statistical difference after 12 week of experiment.2. Change of plasma endotheline and serum nitric oxideITie level of plasma ET of high-lipid control group, low dose lercanidipine-treated group and high dose lercanidipine-treated group is obviously higher than that of normal control group ( P >0.05) , inversely the level of serum NO lower than that of normal control group ( P < 0.05 ) after 8 week of experiment. At the end of experiment the level of plasma ET of high dose lercanidipine-treated group lower than that of high-lipid control group and the level of serum NO high-er than that of high-lipid control group( P <0.05).3. Variety of blood pressure of each group 12 week laterBlood pressure was measuresed at the end of experiment , it did not show significant difference among the group ( P >0.05).4. The immunohistochemical analysis results of VCAM-1The percentage of the positive cell area of VCAM-1 of low and high dose lercanidipine-treated group is significantly less than that of high-lipid control group ( P<0.05).5. the pathologic morphologic changes in aortaObservation by the naked eye and light microscopy showed that the aortic atherosclerotic lesions of lercanidipine-treat...
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