Effect Of Adventitia Applied Slow-releasing Imatinib Mesilate On The Apoptosis And Proliferation Of Vascular Smooth Muscle Cell Of Rat’s Carotid Artery After Carotid Endarterectomy

Objective. To investigate the effect of adventitia applied slow-releasing imatinibmesilate on the apoptosis and proliferation of vascular smooth muscle cells,includingthe changes of construction of vascular wall,and provide new ideas for clinicaltreatment of restenosis after carotid endarterectomy.Methods.96male Sprague Dawley rats,weighted from0.3-0.35Kg,were dividedrandomly as four groups.All rats were fed up with high fat food for two weeks,thenunderwent catotid endarterectomy in left carotid artery. After carotid endarterectomy,the vessel wall was given different treatment.Group A: Perivascular smeared0.5mlsaline; Group B: Perivascular smeared0.5ml30%(w/v%) pluronic F-127gelcontaining3mg imatinib mesilate; Group C: Perivascular smeared0.5ml imatinibmesilate solution（containing3mg imatinib mesilate）; Group D: Perivascular smeared0.5ml30%pluronic F-127gel.The rats were fed up with high fat food after operation.Then8rats of each group were killed randomly on the third,the fourteenth,thetwenty-eighth day after operation.TUNEL was used to find apoptosis VSMCs.PCNAwas used to find proliferating VSMCs. α-SAM and SM22α were used to find thechange of VSMCs phenotype transformation.with HE staining and computer analysisof pathological graph,we caculated the diameter of lumina and thickness of thevascular walls. We counted the positive VSMCs through Image-Pro Plus6.0software.Data were analized by SPSS19.0software,and expressed asmean±SD.Significance was established at p<0.05.Results. The model of rat carotid endarterectomy were successfully constructed.Twenty-eight days after the operation,the luminal diameter and the thickness of the artery,Group B obviously (P＜0.05) in comparison to the other three Groups.The apoptosis rates of VSMCs were increased since three days after operation infour groups. The largest number of apoptotic cells on forteen days after the operation,and then gradually decline. Twenty-eight days after operation,Group B obviously (P＜0.05) in comparison toAand C,D.The positive PCNA VSMCs was found on the three days after operation in allgroups. The largest number of proliferating cells on forteen days after the operation,and then gradually decline.Forteen days after operation,Group B was lower than A,Cand D,the difference was significant.(P＜0.05).SM22α and α-SMA immunohistochemical staining, SM22α, α-SMA-positivecells were in the highest concentrations after three days and then gradually decreased.After28days, SM22α and α-SMA in A, C and D groups have different degrees ofreduction than group B.Conclusions. Adventitia applied slow-releasing imatinib mesilate can elevateVSMCs apotosis rate in carotid endarterectomy model in rats, inhibit VSMCsproliferating rate and inhibit the change of VSMCs’ phenotype transformation.Maybethrough this way,it can reduce the thickness of the injuring vascular prevent it fromrestenosis.so it maybe helpful in treating restenosis after catotid endarterectomy inhuman.