The Research Of Alpha Cyanoacrylate And 5-fluorouracil Compounds In The Application Of Prevention Vein Grafts Restenosis

Objective Coronary artery bypass graft(CABG) has been one main therapy of the coronary heart disease(CHD).However,the restenosis in the postoperation vein draft is an obstacle to the vessle’s patency rate and patients’ prognosis.The absolute extravascular supporting ang local drug delivery of α-Cyanoacrylate( α-CA) and5-fluorouraci(5-fu) have a positive and definite effect.Our group claimed that compound the two factors to be applied in rats’ autologous vein model,which simulating the pathophysiological process after CABG.This study aims at validating its feasibility,and providing new methods.Methods 48 rats(no male or female,aging between 10-12 weeks,weighting between220-280g) were randomised into 4 groups:sham group(S),control group(C), α-CA group and 5-fu group.Each group has 12 rats.S group: just simulating the surgery process;rats’ jugular vein only being dissociated and the lateral branch being ligatured;no dividing;no transplanting.C group:allowing lpsilateral carotid-jugular vein graft. α-CA group:undergoing lpsilateral carotid-jugular vein graft;covering the jugular vein with α-CA glue.5-Fu group:using the α-CA glue and 5-fu mixture.Modeling with modified “CUFF” method.Serum ELISA was carried out at 4time points:T0:pre-operation;T1:immediate postoperative;T2:36 hours after operation;T3:the dead day,4 weeks after operation.ELISA contained EF-1 and TNF-α.4 weeks later,the rats were killed.Then the vein was observed with naked eyes.Being fixed,reserved and HE stained,the fresh vessel’s hyperplasia of its intima,mesolamella and adventitia was observed and determined through microscope and computer image processing software.Through α SMA IHC,we observed the hyperplasia and migration of VSMC;through RT-PCR,αSMA and TNF-α were determined.Results 4 groups all get success.C group:fresh granulation tissue and vein’s expansion can be seen;thickness,edema and light stiffness can be seen as the tube wall.α-CA group:the glue isn’t degraded;some granulation tissues with bright color can be seen.They are easily be separated.They are not expanded obviously,and bounded from the surrounding clearly.The ET-1 has no difference in pre-operation and postoperation.36 hours and 4 weeks later,difference among groupa emerge:36 hours and 4 weeks later,α-CA group、5-fu group and C group’s ET-1 are higher than S group(p<0.05), α-CA group and 5-fu group’s ET-1 are lower than C group(p<0.05);5-Fu group’s(36 hours later) ET-1 are lower than α-CA group(p<0.05).As to TNF-α,all groups descended instantly.36 hours later,C group is lower than S group(p<0.05), α-CA group and 5-fu group are higher than C group(p<0.05).5-fu group(4 weeks later) is higher than α-CA group and C group’s homologous point(p<0.05). When analyzing outcomes analyzed by the computer software,we can see:1.Intima:As for the thickness,C group, α-CA group and 5-fu group is below S group(p<0.05). 5-fu group is lower than α-CA group,C group and S group(p<0.05).2.Mesolamella:C group is higher than S group(p<0.05); α-CA group and 5-fu group is lower than C group(p<0.05).3.Adventitia:C group is higher than S group(p<0.05);5-fu group is lower than C group(p<0.05).Afer implementing αSMA,we can see that:in S group,a small amount of positive cells can be seen in intima and adventitia during 4 weeks.In C group,a large amount of positive cells can be seen in adventitia.In α-CA group,moderate amount of positive cells can be seen,and more can be seen in adventitia.In 5-fu groups,intima’s amount is small and adventitia’s amount is moderate.Thus it can be seen that in C group,lots of smooth muscle cells immigrate to intima and hyperplasia;in α-CA group,smooth muscle cells’ hyperplasia is reduced and the cells immigrate to adventitia.When we test αSMA,we see that:C group expression increased significantly,5-fu group and α-CA group are all lower than C group(p<0.05).Conclusions In antologous vein model in rats,α-CA glue is valid on alleviating draft veins’ hyperphasia of intima and mesolamella and enhancing the potency rate as external support shealth(ESS).The mixture of 5- fu and α-CA is effective in alleviating intima’s hyperplasia and enhancing the patency rate.The mixture of 5- fu and α-CA in autologous vein model in rats is absolutely effective in alleviating intima and mescolamecla’s hyperplasia and enhancing the patency rate.It provides restenosis’ therapy with new thoughts and new methods.