The Experimental Research Of Nanoparticles Mediated Arresten Gene Inhibit The Neointimal Formation Of Vein Grafts

PurposeRecently,we established a new mouse model of venous arterialization by grafting jugular vein to carotid arteries.In many respects,the morphological features of this murine vascular graft model resemble those of human venous bypass graft disease.Using this model,we studied nanoparticles mediated Arresten gene inhibit the neointimal formation of vein grafts.MethodHealthy wistar 30 female rats,the average weight is 250g±10g,were randomly divided into three groups by random number table method.There are 10 rats in each group.Rat models of grafting jugular vein to carotid arteries were established,all the rats before and after surgery were subject to the anticoagulant drugs,but after daily use of low-dose aspirin dissolved in physiological saline(10 mg/kg weight)to fill the stomach,subcutaneous injection different reagents after surgery for 14 days.The model were produced by intraperitoneal injection(1 time per day)of gentamicin for 3 days.The group A(the experimental group):subcutaneous injection nanoparticles mediated Arresten gene0.2ml,The group B(The control group):subcutaneous injection Blank nanoparticles0.2ml,The group C(the blank group):subcutaneous injection saline 0.2ml.2 weeks after the operation,to obtain the venous of objective blood vessel.2 weeks after the operation,to obtain the venous of objective blood vessel.The pathological changes of local vascular tissues and the new intima hyperplasia of experimental vascular segments were observed-by H-E staining.Intima thickness were observed with an optic micro-scope.Using immunohistochemical method to observe the situation of expression of MMP-2.Results30 rat experimental models of autogenous vein graft were established.No major complications and death were encountered during surgery.One of the rats was death,other rats were all have a healthy life in 14 days after the surgery.The activity for the mind and for the body and the diet of rats were normal.The cuts healed well and there were no red and swollen around the incision.There were no exudation around the incision and there were no subcutaneous abscess.When get the transplanted vein,incise the skin according to the original incision.Then we can found that the grafting segment had some adhesion with adjacent tissue.No rupture of blood vessels was noted.These graft vessels had no obvious sign of bacteria infection.There were three rats transplanted vein have been blocked.There had 26 rats,graft vessels were unblocked.The pathological specimens of graft above-mentioned were stained by hematoxylin and eosin and immunohistochemistry.Through the computer-assisted image processing analysis learned that the vascular intimal thickness of the group of nanoparticles mediated Arresten gene was smaller than the control group and blank group,the difference was statistically significant(P<0.05).There was no significant difference between the control group and the blank group(P>0.05).Three groups are visible the expression of MMP-2 in different degrees.The expression of MMP-2 in the group of nanoparticles mediated Arresten gene was less than the control group and blank group(P<0.05),the difference was statistically significant(P<0.05).There was no significant difference between the control group and the blank group(P>0.05).Conclusion1Nanoparticles mediated Arresten gene can reduce intimal hyperplasia in the graft.2We have recently shown that gene reduced intimal hyperplasiais is related to reduce the expression of MMPs-2.And it could inhibit the degradation of extracellular matrix,then inhibit the vascular smooth muscle cell proliferation and migration.The arresten gene can reduce intimal hyperplasia in the graft and retard the restenosis of transplanted vein bridge.It provides a good clinical prospect in the clinical for the ischemic patients of lower extremity who had the long occlusion segment in the lower limb arteries and should not through the intervention treatment.