| Objective:To investigate the effect of hypoxia inducible factor-1 alpha (HIF-1) gene transfection combined with simvastatin on vascular intimal hyperplasia, vascular endothelial cells and smooth muscle cells in vein graft.Methods:40 Wistar rats were randomly divided into 4 groups:combination group (fed simvastatin in the stomach and give HIF1-1 alpha gene transfection in vein grafts), genome group(not feeding simvastatin in the stomach, only give HIF1-1 alpha gene transfection in vein grafts),drug group (only feeding simvastatin in the stomach,without HIF1-1 alpha gene transfection) and control group (not feeding simvastatin in the stomach and not HIF1-1 alpha gene transfection).Each group took internal jugular vein and carotid artery transplantation on the same side, feeding simvastatin in the stomach with the dose of 40mg/kg-D.The vein were taken out after 2 weeks, and observe luminal stenosis through HE stain and Verhoeff elastic fiber stain, using computer image analysis system to calculate and measure the luminal stenosis and the thickness of endometrium respectively.Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting test (Western blot) were used to compare the expression of HIF-1 alpha gene in the four groups, and observe the phenotype of vascular smooth muscle cells (VSMCs) in the transplanted veins and the quantity of muscle-endothelial connected coupling system under the electron microscope. And compare these data quantitatively.Results:Thorough HE staining and elastic fiber staining, the endometrium thickness of combination group,genome,and drug group were significantly suppressed compared with the control group. The expression of HIF-1 mRNA and protein in the combination group (90.8+24.2,10.86+2.76) and genome (89.6+25.3,10.57+2.84) were more significant than that in the drug group (41.2+18.2,3.52+1.90) and control group (42.3+17.3 3.64+2.02)(P< 0.05). The difference is statistically significant,which shows that there was no effect of simvastatin on the expression of HIF-1. Comparing vein graft VSMC contractile phenotyps of the four groups, the combination group (70.7 +10.8) was significantly increased than that in the genome (67.6+10.1), drug group (59.2+11.8) and control group (51.8+12.3) (P< 0.05), and the difference was statistically significant. Compared with the control group, VSMC contraction phenotype in the drug group was significantly increased (P< 0.05), and the difference was statistically significant.Comparing the vein graft VSMC proliferation index of four groups, the index in combination group was lower (14.2+5.7) than that in genome (14.7+5.6), drug group (5.4+8.6) and control group (36.8+9.3) (P< 0.05),and the differences were statistically significant.Comparing the endometrial thickness of vein grafts,the thickness of combination group (17.64+3.54mm) was lower than that in genome (18.73+3.42mm),drug group (30.54+4.02mm) and control group (mm45.25 +3.81) (P< 0.05),and the difference was statistically significant. Comparing the degree of vein graft stenosis in the four groups, the degree in combination group (10.8+3.4%) was lower than that in the genome (12.7+3.6%),drug group (20.8+4.1%) and control group (25.4+4.2%) (P< 0.05),and the difference is statistically significant.Conclusion:1.Through HIF-1 gene transfection combined with simvastatin,the effect of inhibition in hyperplasia of transfected vein graft was much more obvious than that only through simvastatin or only through HIF-1 alpha gene transfection. Its mechanism is mainly through reconstruction of muscle endothelial connection coupling system to exert its effect.2. Symplectic taken orally can inhibit the hyperplasia of autogenous vein grafts,which may due to the cell proliferation of transplanted vascular smooth muscle. The use of statins in the treatment of autologous vein graft has a certain clinical significance to improve the patency rate of the graft.3.Simvastatin has no significant effect on the expression of mRNA and protein of HIF-1 gene. |
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