The Preventive Effects Of Resveratrol And Chinese Red Wine On Experimental Atherosclerosis And Its Mechanisms

Background: Epidemiological studies have showed that moderate consumption of red wine has more beneficial effects than other alcohol beverages in decreasing the mobidity and mortality of coronary heart disease. These findings suggest that red wine posses cardioprotective effects. Recently, the further studies in abroad showed that many effects of red wine are alcohol independent and white wine did not have all those effects. It has been discovered that resveratrol, a polyphenol compound existed in red wine, has many biological activities including antioxidation, antiplatelet and supression of smooth muscle cell proliferation. It may be the primary biological compound existed in red wine and has been studing extensively and increasingly. Studies on the benificial actions of resveratrol or red wine and their mechanism is a hot-spot topic.Red wine could decrease the mobidity of cardiovascular event in patients with atherosclerosis, but the results about whether red wine can prevent atherosclerosis are inconclusive. There are few reports about the effect of resveratrol taken orally on experimental atherosclerosis and we also haven't found the reports about the benificial effects of red wine manufactured in China on human health.Objective: In this study, we will observe the effects of resveratrol or Chinese red wine on: ( 1 ) experimental atherosclerosis in rabbit; (2 ) the endothelial function in experimental atherosclerotic rabbits; ( 3 ) platelet aggregation in experimental atherosclerotic rabbits in vivoand the synthesis of TXB2; ( 4 ) PreproET-1 , iNOS mRNA expression in aortic tissue. With these results, we wish to clarify the preventive effects of resveratrol taken orally on experimental atherosclerosis and its safety and mechanisms and to provide evidence for the practical use of resveratrol. At the same time, we also measure the concentrations of resveratrol in some Chinese red wine and to explore the effects of Chinese red wine on experimental atherosclerosis.Methods: 40 New Zealand male rabbits, divided into 5 groups randomly, were fed with forages as follow respectively: ( 1) normal forage, ( 2 ) high-cholesterol forage (containing cholesterol 1.5%), (3 ) high-cholesterol forage with red wine, (4) high-cholesterol forage with de-alcohol red wine, or( 5 ) high-cholesterol forage with resveratrol. Venous bloods were drawn before experiment and at the end of experiment. Bloods were mixed with various anticoagulants according to different measurement requirement. Plasma was obtained after centrifugation and stored at -20℃or-70℃.1.Measurement of endothelial function in rabbits in vivo: femoral artery diameters were measured both at rest and during reactive hyperemia in two-dimension (2-D) images to calculate the flow-mediated vasodilation (FMD). After a 20 min rest period, 2-D images of the femoral artery were again obtained at baseline and 5 min after sublingual administration of nitroglycerin.2. Atherosclerotic lesion quantification: immediately upon excision, thoracic aortas were fixed in formaldehyde and then immersed in Sudan IV solution. The whole specimen was photographed and plaque area was quantitated using Photoshop 6.0. 5 cross sections (0.4cm-thick) of the aortas were cut in equal appearing interval and subjected to regular histological handling. All slides of specimen were examined using NYD-1000 image analysissystem and intimal and medial layer thicknesses were measured.3. Blood specimen measurement:( 1 ) Lipid: Triglycerides, total and HDL cholesterol were measured by the enzymatic method using OLYMPUS AU2400 biochemical analysis apparatus.(2) Platelet aggregation: ADP-induced platelet aggregation was measured using Bern's method.( 3 ) NO: Plasma NO concentration was measured with nitrate reductase method. The reaction product was quantified on the basis of absorbance at 550 nm.(4) ET-1 and TXB2: Plasma ET-1 and TXB2 were measured with radioimmunoassay method..4. iNOS, ET-1 mRNA expression level: demi-quantitative determ...