| Background and ObjectiveCoronary artery bypass graft(CABG) is one of the most impritmant treatment of Coronary Atherosclerotic Heart Disease(CAD), the great saphenous vein has many advantages,such as:it has the rich source,full length and can be easily acquired,the most importment it has major diameter which is conducive to suture,Since Favaloro the great saphenous vein as graft material,it has become the major clinical transplant material.But various mechanism cause vein grafts restenosis or occlusion which affecsts the service life of vein grafts and reduces Long-term effect. Generally speaking, the long-term patency rate of vein grafts is about80%after one year,75percent after five years, and50%aftwe10years, the annual occlusion rate is2-4%. So some people have to accept the repeated surgery, and the prevention of vein graft stenosis or occlusion has become a research hotspot. Ginsenoside Rbl is a monomer compound extracted from ginseng, it is a calcium channel blockers which can significantly block ICa2+current and reduce right ventricular hypertrophy(RVH) which caused by monocrataline(MCT), it also can resist arrhythmia and the injury of vein grafts caused by hypoxic. It is reported that:Ginsenoside Rb1can inhibit the hyperplasia of vascular smooth muscle cells (VSMCs) by reduce Proliferating Cell Nuclear Antigen(PCNA) and Transforming Growth Factor-beta,(TGF-β) gene expression inthe process of neointimal hyperplasia, and then reduce the synthesis and secretion of extracellularmatrix(ECM),inhibit intimal hyperplasia and extend the service life of the vein graft.The experiment will Establish the animal model in which the external jugular vein of Rabbit will be cut and be sutured to the ipsilateral carotid artery,then inject doses of Ginsenoside Rb1intraperitoneally to observe the changes of vein graft intimal thickness and morphology as well as PCNA and TGF-β gene expression in the three groups. Exploring the effect of ginsenoside Rbl on inhibition of restenosis in vein grafts and its mechanism of action, and providing experimental and theoretical basis for the future clinical applicationsMaterials and MethodsA total of45New Zealand rabbits were randomly divided equally into an experimental group, a model group, and a control group. Endoscopic surgery was utilized to excise their external jugular veins, and then establish an animal model for transplanted vein bridges by anastomosing every unilateral jugular vein end-to-end with the common carotid artery. Removing the vein graft after4weeks, the morphology and thickness of the vein graft intimas were observed under hematoxylin and eosin (HE) staining; the endometrial thickness would be measuredtand the intima/media thickness ratio will be calculated; the PCNA and TGF-(3mRNA expression was also examined using reverse transcription polymerase chain reaction.Results1The results observed by HE staining:The HE-stained sections under light microscopy showed that at4weeks after transplantation, the thickness of vein graft intimas in the experimental group, model group,and the control group were (41.57±2.43) μm,(73.76±7.83) μm,(11.38±0.71) μm, with significant differences among the groups (P<0.05), The intimal/medial thickness ratios of the three groups were (1.21±0.09),(1.44±0.12), and (0.28±0.07), which were significantly different (P<0.05).2The results observed by immunohistochemical stainingPCNA and TGF-(3positive cells can be found in the experimental group, model group and the control group. The Positive cells index of PCNA in the experimental group, model group, and the control group were (35.24±2.31)(57.84±2.79) and (14.37±1.20), The Positive cells index of TGF-(3in the experimental group, model group,and the control group were (30.28±1.69),(52.43±3.85) and (13.57±1.13), with significant differences among the groups (P<0.05).3The results observed by RT-PCR:The RT-PCR results showed that the PCNA and TGF-p mRNA can be found in all the three groups, However,after the intervention of ginsenoside Rbl, the relative expression of PCNA and TGF-β mRNA in the model group was significantly higher than the experimental group and control group.The relative expression coefficients of PCNA and TGF-β were calculated by the ratio of the integrated optical density of the target gene and reference gene. The relative expression coefficients of PCNA mRNA in the experimental group, model group, and control group were (0.942±0.004),(0.756±0.003),and (0.574±0.002), which were significantly different (P<0.05); and the relative expression coefficients of PCNA mRNA in the experimental group, model group, and control group were (0.921±0.006),(0.716±0.003) and (0.539±0.004), with significant differences among the groups (P<0.05).4The results of correlation analysisThe results of Simple linear model in SPSS showed that:(1) PCNA was positively correlated with the restenosis of vein graft and the correlation coefficient was0.402.(2) TGF-P was positively correlated with the restenosis of vein graft and the correlation coefficient was0.376.Conclusion1. The expression of PCNA gene was positively correlated with the degree of vein grafts restenosis.2. The expression of TGF-P gene was positively correlated with the degree of vein grafts restenosis.3. Ginsenoside Rbl can inhibit the over-expression of PCNA and TGF-β gene in the vein graft, reduce the excessive proliferation of vascular smooth muscle cells,which was correlated with the role of reducing the intimal hyperplasia reconstruction of vein grafts. |
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