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Effects Of Lercanidipine On Calcitonin Gene-related Peptide And Endotheline In Atherosclerosis Rabbits

Posted on:2005-04-14Degree:MasterType:Thesis
Country:ChinaCandidate:A M ZhaoFull Text:PDF
GTID:2144360125469761Subject:Internal Medicine
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ObjectionFor the moment, Calcitonin gene-related Peptide is one of the strongest extent blood vessel substance, but endotheline is one of intensly pepite vasoactive activitive polypeptide. Of late years,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 dihydropyridine 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 calcitonin gene-related Peptide and endotheline in atherosclerotic rabbits of lercanidipine on 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 lmg/kg/d; (4) high dose lercanidipine-treated group ( n = 8) : cholesterol-rich diet + lercanidipine 10mg/kg/d. 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 -70X1 deep low temperature refrigerators, unified to detect the values of the serum lipid, ET and CGRP.(2) pathologic specimen: Selected the aorta 5 mmclose 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 SPSS12. 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 calcitonin gene-related PeptideThe 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 CGRP 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 serumCGRP higher 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 pathologic morphologic changes in aortaObservation by the naked eye and light microscopy showed that the aortic atherosclerotic lesions of lercanidipine-treated group are less than those of high dose lercanidipine-treated group , furthermore the high dose lercanidipine-treated group particularly significant.Conclusion1. Lercanidipine can inhibit the elevation of plasma endotheline ,...
Keywords/Search Tags:lercanidipine, Calcium antagonist, atherosclerosis, calcitonin gene-related peptide, endotheline
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