Research On The Effects Of Resveratrol On Vascular Disease Induced By Type2Diabetes And Its Mechanism

Type2diabetes mellitus (T2DM) is associated with an increased risk ofmacrovascular disease such as coronary heart disease and stroke.Epidemiological studies suggest that plant polyphenol resveratrol (REV) isassociated with reduced risk of cardiovascular diseases. However, the effectsof REV on vascular complications in T2DM and its mechanisms have notbeen completely understood. Since chronic inflammatory and endothelialcell activation play a critical role in vascular aging and atherogenesis, weevaluated whether REV can inhibit inflammatory-induced vascular injury inT2DM. We found that REV (50mg/kg/d) can regulate glucose and lipidmetabolism, improve insulin resistance and vascular permeability, andprotect against the foam cells and cholesterol crystals formation in arterialvessel walls of T2DM rats. The protective effects of REV were consistentwith the decrease in nuclear translocation of NF-κB and the downregulationof IL-1β and IL-6lever in blood and TNF-α, ICAM-1, and MCP-1expressions in vascular wall. In addition, REV (10and100nmol/L)treatment protected cultured endothelial cells against increases in the expression of TNF-α, ICAM-1, and MCP-1mRNA and protein induced byhigh glucose via inhibiting nuclear translocation of NF-κB p65. The specificNF-κB inhibitor PDTC-or SiNF-κB p65-mediated downregulation ofNF-κB p65was further enhanced by REV (100nmol/L) in EA.hy926endothelial cells. REV had remarkably suppressed weight gain and loweredthe level of FPG, TC, TG, BUN, SCr, Cys C, and decreased urine protein, andreduced kidney vascular permeability. Increased indices for glomerularinjury were significantly ameliorated by REV treatment．The expressions ofICAM-1mRNA were markedly up-regulated in kidney of diabetic rats,which were effectively suppressed by REV treatment. Western blot andimmunohistoehemistry analysis showed that the expression of ICAM-1wasreduced significantly by REV treatment．In conclusion, these observationssuggest that chronic treatment of T2DM rats with REV attenuates theinflammatory injury of the vascular wall and kidney and these effects areassociated with down-regulation of the NF-κB signal pathway.