Dry Red Wine Preventive Effect On The Prey Of Atherosclerosis And Its Mechanism

Atherosclerosis (AS) takes the first place of the human killers since it leads to massive cardiovascular and cerebrovascular diseases. A number of profound studies have been made for the pathogenesis of AS by many researchers, but the fatality of cardiovascular and cerebrovascular diseases remain still high, which may be due to our doubt on the pathogenesis of AS. As the theory of oxidation modification lipoprotein is generally accepted, the antioxidants attract many interests in the prevention and treatment of AS. Among them, the agents against the oxidation of low-density lipoprotein (LDL) become the most shining ones in this event. A lot of antioxidants exert an anti-atherosclerosis effect by inhibiting the activation of nuclear factor- K B (NF- K B) and then down-regulating the expressions of cytokine protein and mRNA relative to AS. Recent studies showed that dry red wine is rich in polyphenolic compounds and thus shows a strong antioxdative property. It is inferable that dry red wine might play an important role in the prevention of AS. In this study, we attempt to investigate whether dry red wine has preventive and therapeutic effect on cholesterol-fed atherosclerotic rabbits in different stages, and then explore the anti-oxdative effect of dry red wine at cellular, molecular and gene levels, thus provide experimental information and theoretic bases of dry red wine抯 anti-atherosclerosis. Our main findings and conclusions were as follows: 1. With biochemistry, light microscopy and transmission electron III microscopy, it was found dry red wine decreased plasma levels of triglycerido, cholesterol, low-density lipoprotein and increased plasma apolipoprotein A level. The rabbits in dry red wine group (DRW group) had lighter lesion in aortic AS, with less lipid infiltration, smooth muscle cell proliferation, endometrium matrix and elastic fibers, etc in the plaques compared with those in AS group at different time points. These results indicated that DRW had the preventive effect on AS in different stages and reduced its formation and progression. 2. Rapid microdetermination and xanthine oxidase method were used to measure plasma malondialdehyde (MDA) level and superoxide dismutase(S OD)activity. Total radioal梩rapping antioxidative capacity (TRAC) of plasma was obtained with chemiluminescence. The results showed that DRW had strong antioxidative ability, and could decrease the plasma MDA level significantly, increase SOD activity and TRAC and reduce lipid peroxidation, thus it could reduce the proliferation of foam cells. 3. The expressions of monocyte chemotactic protein-i (MCP- 1) and protein kinase C (PKCa) varied in AS plaques of different stages with help of immunohistochemitry, in situ hybridyzation and reverse-transcription polymerase chain reaction. Electrophoretic mobility shift assay (EMSA) confirmed that the increase of NF- K B activity in AS plaque was in a time dependent manner, which was consistent with the elevation of plasma MDA level and the expressions of MCP- I and PKCa. All of these indicated that NF- K B activation, the up-regulated expressions of MCP- land PKCa may take part in AS pathogenesis and development. 4. DRW could significantly suppress the NF- K B activation, down-...