Experimental Study On Local Slow-release Outer Membrane Sirolmus Inhibition Fistula Neointimal Hyperplasia

Objective To establish a model of cimino-brescia arteriovenous fistula by anastomosing rabbit carotid artery with internal jugular vein,we can observe the change of blood vessel structure and TGF-?1,CTGF expression in vascular tissue to explore the feasiblity of mechanism coated with sirolmus in inhibiting the fistula anastomotic intimal hyperplasia.Methods A total of eighteen healthy New Zealand male rabbits weighted 2.2±0.1kg were randomly divided into three groups to establish a model of cimino-brescia arteriovenous fistula by anastomosing rabbit carotid artery with internal jugular vein and gave different disposal route in anastomotic stoma:Blank control group,no management on adventitia and anastomosis site;F-127 group,0.5ml of 20% pluronic F-127 gel was locally applied on adventitia and anastomosis site;F-127 +sirolmus group,0.5ml 20% pluronic F-127 gel containing 0.5mg sirolmus was locally applied on adventitia and anastomosis site.Three weeks after operation,getting close at the anastomotic vein,tissue morphology method to observe the vein intimal hyperplasis and computer image system for measuring the vascular intima tickness;immunohistochemistry and Western blotting method to detect vascular tissue TGF-?1 and CTGF expression.Data were analyzed by using SPSS 13.0statistics software,and were expressed as mean ± SD.Experimental data used ANOVA analysis,if there were significant differences between the groups in line LSD pairwise comparison method,test level ? = 0.05.P <0.05 was considered statistically significant.Results 1.The model of cimino-brescia arteriovenous fistula by anastomosing rabbit carotid artery with internal jugular vein was successful built.2.After 3 weeks of the operation,in pathologically observing,the intima in blank control group and F-127 group thickened obviously as compared with that in F-127+sirolmus group(P<0.05).There's no significant difference between F127 control groups(P> 0.05).3.TGF-?1 expression in immunohistochemistry:TGF-?1was mainly expressed in cytoplasm.After 3 weeks of the operation,blank control group and F-12 7 group were expressed calybank and larger number than F-127+sirolmus group in the vascular intima,media and adventitia.4.CTGF expression in immunohist-ochemistry: CTGF was mainly expressed in cytoplasm.After 3weeks of the operation,blank control group and F-127 group were expressed calybank and larger number than F-127+sirolmus group in endothelial cells lining and outer membrane.5.In Western blotting,TGF-?1 and CTGF had varying degrees in three groups,also they expressed in blank control group and F-127 group were obviously higher than in F-127+sirolmus group(P<0.05).No significant differences in the above parameters were found between blank control group and F-127 group(P>0.05).Conclusion 1.The model of cimino-brescia arteriovenous fistula by anastomosing rabbit carotid artery with internal jugular vein can simulate arteriovenous fistula in human.2.Sirolmus partial paintcoated in vascular adventitia inhibits the fistula neointimal hyperplasia.3.The function of sirolmus' s inhibition is relevant to the expression of TGF-?1 and CTGF,explaining sirolmus can inhibit intimal fibrosis.4.The result of intimal hyperplasia is an process on blood vessels in the outer membrance,intima and intimal.