| Background and Objective:Although multiple types of arterial grafts have been applied to CABG, but it is still very limited in clinical application just because of the lack of supplies. So far great saphenous vein bridge is still the most commonly used blood vessel.but the rate of failure and mortality was increased in diabetic patients after CABG surgery. Currently, the pathogenesis of neointima formation in jugular vein autografts remains poorly understood and no successful clinical interventions have been identified. Ezetimibe is a potent inhibitor of sterol absorption, which selectively inhibits biliary and dietary cholesterol uptake in the small intestine by blocking the Niemann-Pick C1 like 1 sterol transporter activity,thus lowering the serum concentration of total cholesterol and low-density lipoprotein cholesterol (LDL-C).Ezetimibe was also found to reduce monocyte chemoattractant protein-1 expression and decrease macrophage/monocyte content in atherosclerotic plaque in an atherosclerosis rabbit model.Furthermore, ezetimibe enhances acetylcholine-induced endothelium-dependent relaxation through an enhancement of the function of endothelium-derived NO in apolipoprotein E-deficient mice. The Heart and Renal Protection clinical trial demonstrated that lowering of LDL-C with simvastatin plus ezetimibe safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Taken together, these results suggest that ezetimibe may reduce intimal hyperplasia seen in autologous vein grafts. However, this remains to be determined.Results:1, Fifty rats received a vein grafting,5 rats did not establish the graft model and the success rate was 90.00%(45/50, EZ, n=22; NC, n=23). The mortality rate was 8.16%(4/49); 2, Before the surgery, there was no significant difference in intima thickening of the vein grafts between EZ group and NC group (4.34±0.25μm vs 4.54±0.27μm, P>0.05). As compared with EZ group, the thickness of neointima in the vessel walls of the NC rats was significantly greater in 2-week (16.78±4.93μm vs 38.83±5.61μm) and in 4-week (29.53±4.61μm VS 62.45±6.34μm); 3, Immune result shows:There was no positive expression of PCNA in the smooth muscle cells in EZ group and NC group before the surgery.The expression of PCNA in the NC group was significantly increased compared with the EZ group (15.21±5.23 vs 30.5±5.16, at two weeks P<0.01; and9.25±3.34 vs 15.14±1.69 at four weeks, P< 0.05).Conclusions:1, Because of the VSMC proliferation and migration, the thickness of neointima became thicker as early as the day of the autologous vein transplantation in rats; 2, The thickness of the intimal increased significantly in NC group compared with the controls after surgery; 3, It was found that high expression of PCNA after the surgery which maybe a key factor of enhancing the VSMC proliferation and intimal thickening; 4, Ezetimibe may be a new therapeutic target for reducing restenosis of vein grafts in people with diabetes. |
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