Mg—PLGA—rhbFGF复合支架在下肢缺血血运重建中的应用研究  

Application of Mg-PLGA-rhbFGF stent on angiogenesis in hindlimb ischemia

作　　者：包汉梅[1] 刘天军[1] 吕丰[1] 

机构地区：[1]中国医学科学院北京协和医学院生物医学工程研究所 天津市生物医学材料重点实验室,天津300192

出　　处：《国际生物医学工程杂志》2012年第1期33-36,I0002,共5页International Journal of Biomedical Engineering

基　　金：基金项目：天津市自然科学基金项目（09JCYBJC03500）

摘　　要：目的制备荷载生长因子的镁合金-聚乳酸-聚乙醇酸共聚物（Mg-PLGA）复合支架，构建大鼠下肢缺血模型，观察其对缺血骨骼肌血管新生的作用与效果。方法在金属Mg支架表面涂覆包载重组人碱性成纤维细胞生长因子（rhbFGF）的生物降解性PLGA聚合物，制得药物涂层支架（Mg—PLGA-rhbFGF）。体外试验研究支架中药物的释放性能。体内试验构建大鼠下肢缺血模型，机械打孔后植入支架，通过检测Mg2＋在大鼠缺血骨骼肌、血浆、尿液和大便中的浓度，分析支架中的金属Mg在大鼠体内的降解与代谢情况；通过免疫组化分析支架对大鼠缺血下肢骨骼肌血管新生的作用。结果在体外试验中，药物在Mg-PLGA药物涂层支架中具有良好的缓释性能，可持续释放4周。在体内试验中，大鼠血液、尿液和大便中的Mg2＋浓度在正常范围内；免疫组化染色及血管密度定量分析表明，药物涂层支架组与空白支架组相比新生血管显著增多、血管壁增厚。结论载rhbFGF的Mg—PLGA药物涂层支架可促进下肢缺血大鼠缺血骨骼肌血管新生，为危重症下肢缺血性疾病的治疗提供理论基础。Objective To prepare recombinant human basic fibroblast growth factor （rhbFGF） loaded magnesium-poly（D, L-lactide-co-glycolide） （Mg-PLGA） stent and to evaluate its angiogenesis effect in rat model of hindlimb ischemia. Methods The stent was prepared with spiral magnesium （Mg） and loaded with therapeutic agent rhbFGF and PLGA matrix. In vitro drug release study was carried out and the effect was evaluated using a standard animal model of rat hindlimb ischemia. A mechanical drill was conducted and the stent was implanted. The concentrations of Mg2＋ in the muscle adjacent to the stent, rat plasma, urine and stools of the experimental animals were tested to analyze the degradation and metabolism of metal Mg. Immunohistoehemical staining was performed to evaluate the angiogenesis effect of the stent. Results The drug loaded in the stent could release continuously for about 4 weeks. The concentrations of Mg2＋ in the rat plasma, urine and stools were within normal range. Immunohistochemical and quantitative analysis showed that the effect of Mg-PLGA-rhbFGF stem on angiogenesis of rat limb ischemia was better than that of the control group. Conclusion RhbFGF loaded Mg- PLGA stent could promote angiogenesis of rat limb ischemia, and it may provide theoretical basis for the critical patients suffered from lower limb isehemic disease.

关 键 词：镁合金 重组人碱性成纤维细胞生长因子 聚乳酸-聚乙醇酸共聚物 下肢缺血 血管新生 

分 类 号：R318.08[医药卫生—生物医学工程]