Primary Study On Preventive Effects And Mechanism Of Rapamycin Sustained-release Stent In Rabbits Model Of Urethral Stricture

Objective: To explore an effective method for preventing urethral stricture by placing rapamycin sustained-release stent into electric-burned urethral model of rabbit and observing inhibit fibrosis of urethral tissue whether.Methods: In this study,20 adult male New Zealand rabbits were selected and randomly assigned by the number table method.In normal control group,5 rabbits,only ureteroscopy examination was performed.In stenosis model group,5 rabbits,under the ureteroscope,self-made electrocoagulation device was used to ring burn urethra about 10 mm in length and reached muscular layer.In bare metal stent group,5 rabbits,after the electric-burned urethral model was completed according to the method of stenosis model group,bare metal stents were placed at the site of electric-burned under ureteroscope.In rapamycin stenting group,5 rabbits,after model were completed by the same method,rapamycin stents were placed at the site of electric-burned under ureteroscope.After surgery30 days.To evaluate the presence of urethral stricture,displacement and detachment of stents by retrograde urethrography,tissue from the corresponding surgical site was taken for histopathological examination of fibrosis.At the same time,RT-PCR and Western blot were used to detect mRNA and protein expression changes of TGF-?1,Smad3 and MMP1.Results: 1.Status of rabbits in each group: none died of four groups,and no significant changes in animal-behavior were observed after operation.No urethral stricture was observed in normal control group.All rabbits were found obvious urethral stricture in stenosis model group.While in bare-metal stent group,no stents fell off or displacement,and no urethral stricture was found by retrograde urethrography.But stents were difficult to remove under ureteroscopy.In rapamycin stent group,one of stents fell off spontaneously after operation 27 days,while the other 4 stents did not fall off or displacement,and none of the 5 rabbits underwent urethrography showed stenosis formation after stents were removed.2.The proliferation of collagen fibers in rapamycin stent group were significantly reduced compared with bare metal stent group and stenosis model group.Moreover,mRNA and protein of expression levels of TGF-?1,Smad3 were lower than bare-metal stent group and stenosis model group,while the MMP1 expressions was significantly up-regulated(P<0.05).However,between stenosis model group and bare-metal stent group,the expression levels of TGF-?1,Smad3 and MMP1 showed no significant difference(P> 0.05),but higher than normal control group(P<0.05).Conclusion:Rapamycin stents can effectively prevent urethral stricture after electric-burn in rabbits.The mechanism of action may be related to the inhibition of rapamycin on TGF-?1,Smad3 and promotion of MMP1 mRNA,protein expression.The drug sustained-release stents have potential value for the prevention of urethral stricture,which is worth further investigation.