摘要
目的将经脱细胞和肝素处理的小口径异种移植血管结合西罗莫司,旨在进一步改进这种移植血管的性能。方法取新鲜成年犬的颈动脉,经脱细胞和肝素结合处理后分为对照组(经脱细胞和肝素处理)和西罗莫司组(脱细胞和肝素联合西罗莫司处理)。取新西兰大白兔20只,将对照组和西罗莫司组的血管分别移植入同一只兔的左、右侧颈动脉。术后1、2、4、8周采血,采用反相高效能液相层析法(HPLC)检测西罗莫司组中西罗莫司的含量。术后3个月通过超声检查观察移植血管的通畅情况。术后3和6个月分别随机处死10只兔,取双侧血管样本经免疫组织化学和苏木精-伊红(H-E)染色观察血管重塑和内膜增生情况。结果西罗莫司组术后1、2、4、8周血管中均可检测到西罗莫司。术后3个月,对照组有5根移植血管内有斑块形成,斑块发生率为5/20,显著高于西罗莫司组的2/20(P<0.05)。术后3和6个月H-E染色显示,两组部分血管管腔内有血栓形成和内膜增生,对照组吻合口近、远端的内膜厚度和吻合口远端的内膜与中膜厚度比值均显著高于西罗莫司组同时间点(P值分别<0.05、0.01)。术后3个月,免疫组织化学检测显示两组中未形成血栓的移植血管的管壁均可见新生的内皮细胞和平滑肌细胞。结论进一步结合西罗莫司可提高脱细胞和肝素处理的小口径异种移植血管的性能,有效减轻内膜增生,有助于增高血管的远期通畅率,使其可能作为小口径移植血管新的来源。
Objective To develop a new small-caliber decellularized and heparinized vascular xenograft through sirolimus treatment. Methods Oanine carotid arteries were chosen as xenografts through decellularization and heparin treatment. The xenografts with （n = 20, control group） and without （n = 20, sirolimus group） sirolimus coating were implanted in rabbits~ left and right carotid artery, respectively. The content of sirolimus was measured by high performance liquid chromatography （HPLC） at 1, 2, 4, and 8 weeks in sirolimus group. Graft patency was checked by Duplex ultrasonography at 3 months after implantation. Ten rabbits were sacrificed respectively at 3 and 6 months after implantation and bilateral grafts were explanted. Immunohischemical staining and Hematoxylin-Eosin （H-E） staining were used to observe vascular remodeling and intima hyperplasia （IH） of bilateral grafts. Results Sirolimus was found in vascular wall of sirolimus group during 8 weeks after implantation. At 3 months after implantation, plaque formation was found in 5 blood vessels of control group （5/20） but in 2 blood vessels of sirolimus group （2/20, P~ 0. 05）. At 3 and 6 months after implantation, H-E staining showed thrombosis and intimal hyperplasia in some grafts in both groups. The intimal thickness at both anastomotic stomas and the ratio of intimal/medial thickness （I/M） at the distal anastomosis of control group were significantly larger than sirolimus group （P^0.05 or 0.01 ） at 3 and 6 months after implantation. Immunohischemical staining showed that endothelial cells （ECs） and smooth muscle cells （SMCs） covered luminal surface of the grafts without thrombosis at 3 months after implantation. Conclusion Sirolimus treatment can reduce intimal hyperplasia, andhelp to improve the long-term patency of vascular xenograft. The new xenograft may become a new source of small-caliber vascular implantation.
出处
《上海医学》
CAS
CSCD
北大核心
2013年第11期940-943,I0003,共5页
Shanghai Medical Journal
基金
山西省青年科技研究基金资助项目(2009021042-3)
关键词
西罗莫司
内膜增生
小口径
肝素
脱细胞
Sirolimus~ Intimal hyperplasia~ Small caliber~ Heparin~ Decellularization
