生物可降解输尿管螺旋形药物洗脱支架的性能研究  

Characterization of novel biodegradable ureteral drug-eluting stent

作　　者：王鹏超[1] 肖树伟[1] 符伟军[2] 王忠新[2] 洪宝发[1] 张旭[1] 

机构地区：[1]解放军总医院泌尿外科,北京100853 [2]解放军总医院海南分院泌尿外科,海南三亚572013

出　　处：《解放军医学院学报》2016年第5期491-494,共4页Academic Journal of Chinese PLA Medical School

基　　金：北京市自然科学基金项目(7142145);海南省自然科学基金项目(20158299)~~

摘　　要：目的构建一种新型生物可降解输尿管药物洗脱支架,并观察其体内外降解性能、药物释放性能及组织相容性。方法左旋聚乳酸、消旋聚乳酸、雷帕霉素共混后制备两种规格试件。将载药片状试件浸泡于体外尿液环境中,恒温振荡,于2周、4周、6周、8周、10周、12周时通过形态观察、质量变化、电镜扫描研究试件的体外降解性能;采用高效液相色谱法测定试件载药量变化以研究其药物释放性能。将螺旋型药物洗脱支架置入兔背部肌肉内,于1周、4周、12周时行组织学观察评价支架的组织相容性。结果载药片状试件体外尿液恒温振荡环境下,6周时可见少量白色漂浮物,质量丢失率约15%,扫描电镜观察试件表面可见细小孔洞;12周时完全降解为泥沙样沉积物。高效液相色谱结果 :初始组(1 425±47)μg,2周组(1 400±23)μg,4周组(1 368±55)μg,6周组(1 278±88)μg,8周组(780±32)μg,10周组(362±36)μg。初始组与2周组、2周组与4周组组间差异均无统计学意义(P>0.05);6周组明显低于4周组(P<0.05);8周组与10周组分别低于其前一时间组(P<0.01)。兔背部肌肉置入后,组织学观察术后炎症反应轻微,12周时纤维增生不明显。结论新型生物可降解输尿管药物洗脱支架具有良好的降解性能、药物释放性能和组织相容性。Objective To build a new biodegradable ureteral drug-eluting stent（DES）, and investigate its degradation characteristics, drug release property and histocompatibility in vivo and vitro. Methods Two typical specimens were constructed with Poly-L-Lactide（PLLA）, Poly-DL-Lactide（PDLLA） and rapamycin. The flaky specimens were dipped into fresh urine sample with gentle agitation in vitro. Scanning Electron Microscope（SEM） and mass measurement were performed to investigate the biodegradation characteristics of stents, and High-Performance Liquid Chromatography（HPLC） was performed to investigate the drug release property of stents at 2, 4, 6, 8, 10, 12 weeks after agitation. The DES was implanted in the dorsal muscle of 6 rabbits. The histocompatibility of DES was assessed by histology and image analysis system at the first, fourth and twelfth week. Results After being dipped in human urine for 6 weeks, a few of white floaters were found and the weight of flaky specimens were decreased by 15%. Under the SEM, small holes were found on the surface of specimens. The drug loading of initial state, 2, 4, 6, 8 and 10 weeks group were（1 425±47） μg,（1 400±23） μg,（1 368±55） μg,（1 278±88） μg,（780±32） μg and（362±36） μg, respectively. There were no significant differences in drug loading between initial state and 2 weeks group, 2 weeks group and 4 weeks group（P〉0.05）. Meanwhile, the drug loading of 6 weeks group detected by HPLC was significantly lower than 4 weeks group（P〈0.05）, and the drug loading of 8 weeks group and 10 weeks group were significantly lower than that of the former groups（P〈0.01）. The results of histology showed that the acute inflammatory reactions were mild and the fibrous tissue proliferated slightly at the twelfth week. Conclusion The degradation characteristics, drug release property and histocompatibility of new biodegradable ureteral drug-eluting stent can meet the requirements of the repair of human ureteral injury.

关 键 词：输尿管 生物可降解 药物洗脱支架 

分 类 号：R693.5[医药卫生—泌尿科学] R318.08[医药卫生—外科学]