局部外膜缓释西罗莫司对内瘘血管内膜增生的影响

Effect of local slow-release coated sirolmus on fistula neointimal hyperplasia

目的建立兔颈总动脉-颈内静脉内瘘模型;探讨血管外膜涂层缓释西罗莫司对内膜增生的影响。方法健康雄性新西兰大耳白兔18只,随机分为对照组、F-127组和F-127+西罗莫司组,每组6只,将兔颈总动脉与颈内静脉端吻合,建立内瘘模型后,按组别在吻合口进行不同处理:对照组,不给予任何处理;F-127组,涂抹20%pluronic F-127多聚凝胶0.5 m L;F-127+西罗莫司组,涂抹携带西罗莫司0.5 mg的20%pluronic F-127多聚凝胶0.5 m L。术后3周,获取近吻合口处静脉血管,采用苏木精-伊红染色法观察静脉内膜增生情况,测量静脉血管内膜厚度。采用免疫组织化学法及Western blotting法检测各组转化生长因子β1(TGF-β1)和结缔组织生长因子(CTGF)的表达。结果术后3周,对照组和F-127组较F-127+西罗莫司组血管内膜增生明显(P<0.05);对照组和F-127组较F-127+西罗莫司组TGF-β1和CTGF表达明显升高(P<0.05),对照组与F-127组之间差异无统计学意义(P>0.05)。结论西罗莫司血管外膜涂层缓释可有效抑制内瘘血管内膜的增生;西罗莫司可通过抑制TGF-β1和CTGF的表达来抑制血管内膜纤维化过程。

Objective To establish a model of cimino-brescia arteriovenous fistula by anastomosing rabbit carotid artery with internal jugular vein and to explore the mechanism of coated sirolmus in inhibiting the fistula anastomotic intimal hyperplasia. Methods A total of 18 healthy NewZealand male rabbits were randomly divided into blank control group（ the grafts accepted no management）,F-127 group（ 0. 5 m L of 20% pluronic F-127 gel was locally applied on adventitia and anastomosis site） and F-127 ＋ sirolmus group（ 0. 5 m L 20% pluronic F-127 gel containing 0. 5 mg sirolmus was locally applied on adventitia and anastomosis site） to establish models of cimino-brescia arteriovenous fistula by anastomosing rabbit carotid artery with internal jugular vein. Three weeks after operation,the anastomotic veins wereharvested. The vein intimal hyperplasis was observed with tissue morphology method,the vascular intima thickness was measured with computer image system,and expressions of TGF-β1 and CTGF were detected with immunohistochemistry and western blotting. Results Three weeks after operation,the intima in the blank control group and F-127 group thickened obviously as compared with that in F-127 ＋ sirolmus group（ P〈0. 05）. The TGF-β1 and CTGF expression were higher in the blank control group and F-127 group than in the F-127 ＋ sirolmus group（ P〈0. 05）. There were no significant differences in the above parameters between the blank control group and F-127 group（ P〉0. 05）. Conclusion Sirolmus partial paintcoated in vascular adventitia inhibits the fistula neointimal hyperplasia via inhibition of TGF-β1and CTGF expressions.