| ObjectiveTo explore the regressive effect of moderate alcohol consumption and captopril in the cholesterol-fed rabbits carotid atherosclerosis (CAS) models, and advanced study antiatherosclerotic mechanisms in biochemistry, pathology and molecular biology in order to provide a scientific basis for using moderate alcohol and captopril in the prevention of atherosclerosis.MethodsIn this study, we used healthy male New Zealand rabbits which were weighted 2.20±0.15kg,and were 3-4 months old. Forty rabbits were divided randomly into two groups: carotid atherosclerosis(CAS) models group(32 rabbits) with a high fat diet (containing 1% cholesterol,2% yolk,2% lard and 95% normal animal feeds)and normal group (8 rabbits). After 10 weeks of induction,8 CAS rabbits were killed as a positive control arid the other 24 CAS rabbits were divided randomly into three groups;(1) Spontaneous regression group,which was fed with normal animal feeds;(2)Moderate alcohol consumption group,which was fed with normal animal feeds and moderate alcohol intake with 0.6g·kg-1·d-1;(3)Captopril group,which was fed with normal animal feeds and Captopril with 2.5mg·kg-1·d-1. After six weeks of treatment,intima-media thickness,plaque area(PA) and carotid artery stenotic degree were observed in all the groups by HPIAS-1000 hypsi-lampros chromatic color patho-image analysis system,and the expression of NF-kappaB p65 was determined by immunohistochemistry analysis. Additionally,total Cholesterol(TCH), triglyceride (TG),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol(LDL-C) and glucose (GLU) in serum were assayed by automatic biochemistry analyzer at the initial experiment and the end of 10 weeks,13 weeks and 16 weeks.ResultsThere was no difference in serum cholesterol level among the three high-cholesterol groups(P>0.05),but they were much higher than those of the normal diet group(P<0.01) at the end of 10 weeks.TCH,TG,LDL-C and GLU concentrations in carotid atherosclerosis (CAS) models group were decreased, but they were still higher compared with those of normal diet group(P<0.01) at the end of 13 weeks.An increase of HDL-C and an degression of TCH and LDL-C were obviously much higher in the moderate alcohol consumption group than in the spontaneous regression group and captopril group (P<0.05),but there was no difference in serum cholesterol level between the spontaneous regression group and captopril group(P>0.05)at the end of 13 weeks and 16 weeks.In normal group,no atherosclerosis plaque was formed in carotid artery tunica intima vasorum,but there existed lots of atherosclerosis plaque among the three high-cholesterol groups. A lot of foam cells in carotid atherosclerosis plaque.Compared with those in normal group,the vascular intima media thickness(IMT),carotid artery plaque area and the degree of angiostegnosis increased obviously(IMT:4.25±0.89μm vs 24.88±2.90μm,18.25±1.67μm, 14.50±1.60μm,14.88±1.89μm; PA:0μm2vs 1600.25±2761.42μm2,19946.50±1217.21μm2, 17964.63±538.45μm2,17545.50±1131.54μm2;degree of angioste-gnosis:0 vs (4.91±0.51)%, (2.82±0.20)%,(2.49±0.26)%,(2.53±0.17)%,respectively,(P<0.01) in the tenth week killed rabbits group,spontaneous regression group,moderate alcohol consumption group and captopril group.The vascular intima media thickness(IMT),carotid plaque area and the degree of angiostegnosis all decreased among the three carotid atherosclerosis(CAS) model groups;However,compared with those in Spontaneous regression group,the vascular intima media thickness decreased markedly(P<0.05) in the moderate alcohol consumption group and captopril group. In addition,there was no positive expression of nuclear factor-kappaB in the normal diet group,but there which was strong expression of nuclear factor-kappaB in the CAS model group.Compared with those in the tenth week killed rabbits group,the expression of nuclear factor-kappaB decreased significantly in the Spontaneous regression group,moderate alcohol consumption group and captopril group[(42.73±2.81)% vs (22.95±2.36)%,(16.68±1.67)%,(16.06±1.88)%,respectively.P<0.05];Furthermore,the expre-ssion of nuclear factor-kappaB was significantly weaker in the moderate alcohol consumption group and captopril group than in the Spontaneous regression group (P<0.05),and there was no difference between the moderate alcohol consumption group.and captopril group.Conclusions1. The rabbit's CAS models could be made by giving simple high lipid animal feeds. Such method was safer,more scientific and exacter than damaging endothelium.Furthermore the method was in line with CAS's natural formation process.2. The CAS plaques were formed easily at carotid artery crotch. Moderate alcohol consumption and captopril could decrease significantly the vascular intima media thickness,plaque area and the degree of angiostegnosis, and exert an effect of antiathero-sclerotic mechanisms and have similar effect.3. Moderate alcohol intake and captopril both could have regressive effect on carotid atherosclerosis in the cholesterol-fed rabbits,and there were no significant differences in the functions and effects between them.4. Moderate alcohol intake could all increase serum HDL-C concentration,and decrease TCH and LDL-C concentration notably,but had no effect on a TG.,Which may be one of its antiatherosclerosis methods,Captopri had no effect on lipid metabolism.5. Nuclear factor-kappaB avtivation was a key step to cause inflammation and oxidative stress,so it is important to decrease nuclear factor-kappaB avtivation in order to control inflammation and oxidative stress.Moderate alcohol consumption and captopril both could decrease significantly the positive expression of NF-κB.The results suggested that moderate alcohol consumption and captopril could perform the antiatherosclerosis function by decreasing the positive expression of NF-κB and extinct carotid atherosclerosis plaque. |
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