| ObjectiveCoronary 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 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.Methods72 rats(no male or female,aging between 10-12 weeks,weighting between220-280g) were randomised into 6 groups:sham group(S),control group(C),α—cyanoacrylate group(α-CA),Rapamycin group(RPM),DMSO group and SB203580 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.RPM group:using the α-CA glue and RPM mixture.DMSO group:the vein with DMSO;the vein with α-CA glue;giving instragastric administration one hour before surgery.SB203580 group:the vein with DMSO(SB203580contained,5mg/kg);the vein with α-CA glue;giving instragastric administration one hour before surgery;modeling with modified “CUFF” method.Serum ELISA was carried out at 4 time 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.4weeks later,the rats were killed.Then the vein was observed with naked eyes.Beingfixed,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 αSMA IHC,we observed the hyperplasia and migration of VSMC;through RT-PCR,αSMA and TNF-α were determined.Results6 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 4weeks later,difference among groupa emerge:36 hours and 4 weeks later,α-CA group、RPM group and SB group’s ET-1 are lower than C group(p<0.05);RPM group(4 weeks later) and SB group’s(36 hours and 4 weeks later) ET-1 are lower than α-CA group(p<0.05).As to TNF-α,SB group and RPM group can be seen a slow rise instantly,other groups descended instantly.α-CA group(36 hours later),RPM group(instantly) and SB group(instantly,36 hours and 4 weeks later) are all higher than 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,SB group is below C group,RPM group and DMSO group(p<0.05).RPM group and SB group are lower thanα-CA group(p<0.05).2.Mesolamella:C group is higher than S group(p<0.05);C group is higher than α-CA group,RPM group and DMSO group(p<0.05).3.Adventitia:C group is higher than S group(p<0.05);RPM is lower than C group(p<0.05);SB group is lower than C group,α-CA group and DMSO group(p<0.05).After implementingαSMA,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 and DMSO group,moderate amount of positive cells can be seen,and more can be seen in adventitia.In SB and RPM 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.In SBgroup,with RPM’s intervention,cells’ hyperplasia is lower and cells immigrate to adventitia.When we test αSMA,we see that:SB group,RPM group and α-CA group are all lower than C group(p<0.05);SB group and RPM group are both lower than α-CA group and DMSO group(p<0.05).ConclusionIn 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).RPM as local drug delivery on SDP,it is effective in alleviating intima’s hyperplasia and enhancing the patency rate.The inhabitor--P38 MAPK and the local drug--SB203580 also do the same effect.Applying SDP in autologous vein model in rats is absolutely effective in alleviating intima and mescolamecla’s hyperplasia and enhancing the patency rate.It proves that the new SDP system’s validation and feasibility is no doubt.It provides restenosis’ therapy with new thoughts and new methods. |
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