肝素化PCL／PLGA降解支架远期体内特性  

Investigation of long-term results of heparinized polycaprolactone/poly D, L-lactic-glycolic acid scaffold in vivo

作　　者：赵健[1] 程兆云[1] 权晓强[1] 赵子牛[1] 吕丰[2] 刘晓程[3] 

机构地区：[1]河南省人民医院郑州大学人民医院心血管外科,450003 [2]天津生物医学工程研究所生物材料重点实验室 [3]天津泰达国际心血管病医院

出　　处：《中华胸心血管外科杂志》2013年第10期620-623,共4页Chinese Journal of Thoracic and Cardiovascular Surgery

基　　金：河南省科技厅重点科技攻关项目（122102310073）;天津市科技发展计划项目（05YFGZSF02900）

摘　　要：目的研究肝素化的聚己内酯（Polycaprolactone，PCL）／聚乳酸乙醇酸（PolyD，L-lactic-glycolicacid，PLGA）双层降解支架体内远期结构稳定性及开放性。方法建立小型猪急性心肌梗死模型，设立空白支架对照组（Bs组）、空白支架＋骨髓间充质干细胞移植（MSCs）组（BS-MSCs组）、肝素化支架（HS）＋骨髓间充质干细胞移植组（HS-MSCs组）。甲苯胺蓝分光光度法绘制支架内肝素体外释放曲线，6个月后连续切片结合3D-DOCTOR软件重建支架管腔轮廓，扫描电镜评价支架内皮化，组织学染色观察支架周围血管新生及支架降解后胶原纤维重塑情况，Western印迹法量化支架内皮细胞环氧合酶（Cyclooxygenase，COX-1／COX-2）和前列腺素合成酶（ProstacyclinSynthase，PGIS）的表达情况，ELISA法量化血浆前列腺素（Prostacyclin，PGI2）和血栓素（Thromboxane，TXA2）的含量。结果4周时支架内约89％的肝素释放，6周时完全释放。6个月时三维重建显示支架轮廓清晰，无明显变形，管腔被内皮细胞覆盖，周围见大量存活心肌及新生血管，支架降解后空间被新生胶原纤维重塑。HS-MSCs组和BS．MSCs组PGIS的表达及血浆PGI2含量较BS组显著增加（P〈0．01和P〈0．05）；HS-MSCs组COX-1的表达及TXA：的含量较BS-MSCs组、Bs组显著减少（P〈0．01），后两组间差异无统计学意义（P〉0．05）。结论6个月后支架轮廓无明显变形，管腔被内皮细胞覆盖，通过PGI2达，保证支架的内源性抗凝活性。Objective Biodegradable polycapmlactone （PCL）/poly D, L-lactic/glycolic acid （PLGA） scaffold is a promising modality for diffuse coronary atherosclerosis diseases unavailable to bypass graft. The purpose of this study was to e- valuate the long-term performance of PCL/PLGA scaffold in vivo following polymer degradation. Methods Two scaffolds with and without heparin modification [ Heparinized Scaffold （HS） and Blank Scaffold （BS） ] were implanted. Except for control group, bone marrow mesenchymal stem ceils （MSCs） were also transplanted around the scaffold. Animals were grouped into control BS group, BS-MSCs group and HS-MSCs group （each n = 6） and survived 6 months. Patency and integrity of scaffold were evaluated by echoeardiography and 3D-DOCTOR software. Endothelium coverage of the lumen was evaluated by scanning electron microscopy. Neovessles and collagen fiber within the scaffold were identified by histological staining. Prostacyclin （PGI2 ） and thromboxane （TXA2 ） production in the plasma were measured by ELISA. The expression of cyclooxygenase （ COX-1, COX-2） and prostacyclin synthase PGIS was detected by Western blot. Results The heparinized scaffold kept pa- tent up to 6 months and the lumen was covered by confluent endothelial cells. Histological staining revealed remodeling of colla- gen fiber and reconstruction of neovascular network immediately around the lumen. PGI2 production and PGIS expression in BS- MSCs group and HS-MSCs group significantly increased compared with BS group （ P 〈 0.05 and P 〈 0.01, respectively）. Nonetheless, TXA2 production and COX-1 expression in BS-MSCs group was more pronounced than HS-MSCs group （ P 〈 0.01 ） , showing no difference between BS-MSCs and BS group （ P 〉 0.05 ）. Conclusion Despite polymer degradation and en- tire hepafin release, the scaffold could continuously keep the structual integrity and lumen patency until 6 months by reinforce- ment of host collagen fiber and PGI2 expression.

关 键 词：冠状动脉疾病 支架 前列腺素 肝素 内皮细胞 

分 类 号：R654.2[医药卫生—外科学]