Antiatherogenetic And Anti-lipoperoxidative Effects Of Lercanidipine In Cholesterol-fed Rabbits

ObjectiveCardiovascular and cetebrovascular disease is the common illness, which endanger human heath. Atherosclerosis (AS) is their common pathological foundation. AS is a chronic and complex process. With the study for the patho-genesis of AS, many investigations have been showed that the oxidative procedure mediated by free radical and its products exert an important role in athero-genesis. Calcium antagonists is one of the commonly used cardiovascular drugs in clinic. Mass study evidences show multi-calcium antagonists posses antia-therogenetic effect. Lercanidipine is the high vessel-selective dihydropyridine calcium antagonist. Lercanidipine has been shown in vitro to interfere with SMC cell proliferation and migration. Lercanidipine can intervene atherogenesis. We creat AS animal model through cholesterol-fed rabbits and to probe the anti-early AS and anti-lipoperoxidative effects of lercanidipine. We hope to provide the new idea for early prevention of clinical cardiovascular disease.Methods1. Animal model: 32 white rabbits (male or female;2. 0 0. 5Kg;4-6 months ). All the animals were randomized into 4 groups: control group (n = 8 ) , treated with normal diet; high lipid group ( n = 8 ) , treated with high cholesterol diet (contain 1% cholesterol powder + 7.5% yolk + 2% lard) ; lercanidipine low dosage group ( n = 8) , treated with high cholesterol diet plus lercanidipine 1 mg/kg/d; lercanidipine high dosage group ( n = 8 ) , treated with high cholesterol diet plus lercanidipine 10mg/kg/d;Each rabbit total diet 150 g/d for 12 weeks.2. Determination of blood sample; The sample were collected from the pe-ripheral vessel4 times (before high lipid diet, 4 week, 8 week, 12 week). The concentration of TC, TG, HDL-C, LDL-C, SOD, MDA were detected.3. Determination of blood pressure (SBP, DBF) and heart rate(HR) : At the end of 12 weeks after lercanidipine treated, the rabbits were anesthetized with Urethan (5ml/kg) . The right carotid artery was cannulated with a te for the measurement of blood pressure. The te was connected with pressure transducers and the SBP,DBP,HR were recorded with the polysiogical system.4. Pathological analysis: The part of the thoracic aorta was cut off and divided into two parts. One part of the vessel specimen was dehydrated, embedded and section-cut for morphological studies. Morphological studies include HE staining, elastic fibers staining, the lumen area, lipid plaque cross section area were detected by MetaMorph Image System after staining. The other part of thoracic aorta was used for determination of aorta SOD activity and MDA production.5. Statistic analysis; All the data were expressed as mean valus 卤 standard deviation. Statistic analysis were done using SPSS 10. 0 ststistical software. Comparison among 4 groups was tested by ANOVA and comparison between 2 groups was tested by SNK test, P values less than 0. 05 were considered to be significant.Result1. The change of blood lipidThe level of TC, LDL-C increased after high lipid diet comparing with that of control group ( P <0.01) , but the level of TC, LDL-C had no difference a-mong 3 high lipid diet group( P > 0. 05 ). The level of TC among 4 groups had no significant change ( P > 0.05 ).2. The change of serum SOD and MDAAt the end of 12 weeks, compared with the high lipid group, the level of serum SOD of lercanidipine ( Img/kg/d) group and lercanidipine (10mg/kg/ d) group was significantly increased (P <0. 05) , inversely the level of serum MDA of lercanidipine (Img/kg/d) group and lercanidipine (10mg/kg/d)group was significantly decreased ( P < 0.05).3. The change of aorta SOD and MDAThe level of aorta SOD of lercanidipine (10mg/kg/d) group was higher than that of high lipid group (P <0. 05) , inversely the level of aorta MDA of lercanidipine ( 10mg/kg/d) group was lower than that of high lipid group (P <0. 05).4. The change of BP and HRThe level of BP and HR among 4 groups had no difference( P > 0.05).5. The change of vascular morphologyRes...