The Effect Of Genistein On Vascular Remodeling Of Rabbit Undergoing Carotid Endarterectomy And Autogenous Vein Graft

Objective:1 To construct the rabbit carotid endarterectomy and autogenous vein graft restenosis models,and fix in situ perfusion,then evaluate the effect of 20mg/kg genistein on vascular remodeling(VR) of rabbit carotid endarterectomy and autogenous vein grafts.2 To construct the rabbit carotid endarterectomy and autogenous vein graft restenosis models which get 20mg/kg genistein,evaluates the expression of MMP-2 in vascular endothelial cell and the level of NO,ET-1 in plasma.Materials and methods:1.The subjects are Fifty-six adult male New Zealand white rabbits which are sub-six-month-old and undergoing carotid endarterectomy and autogenous vein graft,including one group of twenty-eight used ordinary diet,contrasting the other group of twenty-eight intervented 20mg / kg genistein.The left carotid artery endarterectomy and anterior vein autogenous vein grafts are restenosis model,the contralateral sham-operated carotid arteries and the anterior veins are the controls model.Four observation time points are 3 d,7 d,14 d,42 d after admission,each time point clicks seven animal models.First,collect blood,then fix the vascular in situ perfusion.2.Pathological analysis:Make films by HE,Masson staining and analyze morphologically.3.Immunohistochemical analysis:Evaluate the expression of MMP-2 at 3 d,7 d,14 d,42 d.4.Chemical analysis:Evaluate the level of NO by Separately collecting plasma before surgery and 3d,7d,14d,42d after sugery.5.Radio-immunity analysis:Measure the level of ET-1,the used kit is provided by Beijing Poole Kit Albert Biology Technology Ltd.Results:ⅠThe effect of genistein on vascular remodeling of the carotid endarterectomy and autogenous vein graft rabbit.1.Generally speaking,Vein graft lumen area(LA) was gradually shrinking after Endarterectomy and autogenous vein graft,the 3 days group had a significant increase than the control group,LA of the 7 days,14 days,42 days group were significantly decreased than the control group.The veins showed the formation of elastic fibers.Genistein can inhibit the contraction of vein graft remodeling.The Genistein group had no significant difference with the control group at 3 days,the LA was significantly increased than the ordinary diet group at 14 days and 42 days.Genistein can effectively inhibit the contraction vascular remodeling(P＜0.05). 2.The external elastic plate area of the proximal anastomotic stoma had a decreased trend after the endarterectomy and autogenous vein graft.It showed the contraction vascular remodeling and the partial membrane formation at 3 days and 7 days;The lumen of proximal anastomotic stoma in carotid artery was significantly reduced at 14 days and 42 days,at the same time,the complication of vascular contraction and plaque formation occurred.Genistein can inhibit the contraction of vein graft remodeling.The lumen of the Genistein intervention group had no significant difference contrasting the control group at 3 days(P＜0.05).The contraction both intra-elastic and the extra-elastic plate were less than the control group at 7 days(P＜0.05).The trend was more significant at 14 days and 42 days,and the hyperplasia of VSMC reduced,so inhibit the contraction vascular remodeling efficiently(P＜0.05).ⅡThe effect of genistein on the expression of MMP-2,NO,ET-1 of the carotid endarterectomy and autogenous vein graft rabbit1.The NO showed low expression at 3 d,7 d,14 d,the NO at 42d is similar to the normal contrast group.To the Genistein group,the expression at 3 d,7 d,14 d is higher than the ordinary diet group,but is lower than the normal contrast group.It had no significant difference between the Genistein group and the normal contrast group at 42d2.The ordinary diet group,the expression of ET-1 was high at 3d and 7d,fell down at 14 d, decreased further at 42d,but still higher than the normal contrast group,genistein can inhibit the expression of ET-1.3.The MMP-2 also expressed in uninjured vessel wall,mainly in VEC.It had a weak expression in VSMC.The peak expression of MMP-2 appeared at 14 days.It had obvious relevance between the total expression rate of MMP-2 on each vessel wall and the corresponding vascular remodeling.Genistein can inhibit the expression of MMP-2.Conclusion:1.The experiment has successfully constructed the rabbit carotid artery endarterectomy and autogenous vein graft restenosis model.2.The process of arterial restenosis exists contractile remodeling situation,the narrow lumen depends on the change of vascular remodeling index.IELA and EELA are the indexes of evaluating luminal stenosis and vascular remodeling.Genistein can significantly reduce the contraction of vascular remodeling.3.The expansion and contraction exists the remodeling situation and the process of vein graft stenosis,genistein can significantly reduce the vein remodeling and the intimal hyperplasia.4.Genistein can inhibit the expression of MMP-2,ET-1,but increase the expression of NO, so reduce incidence of the restenosis.