杨梦毅,黄楠,熊开琴,杜泽煜,马青,徐佳乐,汪川哲,涂秋芬.促内皮和抗炎的丹参酮IIA洗脱支架涂层研究[J].表面技术,2024,53(6):222-233.
YANG Mengyi,HUANG Nan,XIONG Kaiqin,DU Zeyu,MA Qing,XU Jiale,WANG Chuanzhe,TU Qiufen.Pro-endothelial and Anti-inflammatory Tanshinone IIA-Eluting Stent Coating[J].Surface Technology,2024,53(6):222-233 |
| 促内皮和抗炎的丹参酮IIA洗脱支架涂层研究 |
| Pro-endothelial and Anti-inflammatory Tanshinone IIA-Eluting Stent Coating |
| 投稿时间：2023-03-17 修订日期：2023-05-05 |
| DOI：10.16490/j.cnki.issn.1001-3660.2024.06.021 |
| 中文关键词: 丹参酮IIA 药物洗脱支架 促内皮 抗炎 抗血栓 血管细胞相容性 |
| 英文关键词:tanshinone IIA drug-eluting stent pro-endothelial anti-inflammatory anti-thrombosis vascular cytocompatibility |
| 基金项目: |
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| Author | Institution |
| YANG Mengyi | Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| HUANG Nan | Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| XIONG Kaiqin | Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| DU Zeyu | Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| MA Qing | Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| XU Jiale | Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| WANG Chuanzhe | Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| TU Qiufen | Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
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| 中文摘要: |
| 目的 针对目前临床心血管支架存在的晚期血栓和支架内再狭窄等问题，通过超声雾化喷涂技术构建传统中药丹参酮IIA(TS)洗脱支架，探究其在动脉粥样硬化病变部位的治疗作用。方法 采用超声雾化喷涂技术构建TS洗脱支架;利用水接触角(WCA)检测仪、傅里叶变换红外吸收光谱仪(FTIR)、球囊扩张实验及场发射扫描电镜(SEM)等对涂层表面的亲疏水性、化学成分及结构、涂层机械性能进行检测分析;采用紫外-可见光分光光度计(UV-Vis)对TS涂层药物释放行为进行检测;通过体外溶血率和血小板实验初步评价涂层的血液相容性;通过体外细胞相容性实验评估TS涂层对内皮细胞(ECs)和平滑肌细胞(SMCs)增殖的影响，以及对巨噬细胞炎症行为及表型的调节作用;通过半体内血液循环实验进一步探索涂层抗血栓形成效果。结果 WCA、FTIR、SEM和UV-Vis等检测结果证实了TS洗脱支架的成功制备，涂层中TS在体外能够保持28 d持续释放;体外生物相容性结果表明，TS与聚乳酸-羟基乙酸共聚物(PLGA)质量比为30%的涂层具有显著抑制血小板的黏附和激活、促进ECs及抑制SMCs增殖的作用，同时能够有效调节巨噬细胞的炎症行为;半体内血液循环实验结果表明，涂层具有良好的抗血栓形成的效果。结论 制备的TS洗脱支架具有选择性促进内皮增殖，抑制平滑肌增生、调控炎症的作用，以及优异的抗血栓形成能力，能够为病变血管修复提供一种潜在的解决方案。 |
| 英文摘要: |
| Cardiovascular disease is one of the most common causes of death worldwide and is widely recognized as the leading killer of human health. Cardiovascular stent intervention is currently the primary treatment for cardiovascular disease. The most widely used drug-eluting stents (DES) reduce the incidence of restenosis to approximately 3%-20% based on bare metal stents (BMS), but the released drugs inhibit endothelial proliferation while impairing the function of the endothelial layer, causing a series of cellular dysfunctional events such as thrombosis, abnormal proliferation of smooth muscle cells (SMCs), inflammatory response, delayed re-endothelialisation and even the development of advanced neoatherosclerosis. To address these issues, an ideal vascular stent should have multiple biological functions such as promoting the proliferation of endothelial cells (ECs), inhibiting the overproliferation of SMCs, regulating inflammation and being antithrombotic. Tanshinone IIA (TS) is one of the most pharmacologically active components isolated from the traditional Chinese medicine Salvia miltiorrhiza, which has anti-atherosclerotic, anti-inflammatory, antioxidant and anti-thrombotic effects. In order to maintain the active structure of TS during application, TS-eluting stents were prepared by ultrasonic atomisation spraying and its therapeutic effects in atherosclerotic site were explored. A coating carrier, polylactic acid-hydroxyacetic acid copolymer (PLGA), which had excellent physical strength, controlled degradation properties and the ability to contain large amounts of drug without altering the degradation pattern was selected. Water contact angle (WCA) detector and Fourier transform infrared absorption spectrometer (FTIR) were selected to examine the hydrophobicity, chemical composition and structure of the coating surface, and the mechanical properties of the coating on the stent surface were evaluated by means of balloon expansion experiments and field emission scanning electron microscopy (SEM) observations. The drug release behavior of the coating was examined by an UV-Vis spectrophotometer. The haemocompatibility of the coating was initially evaluated by in vitro haemolysis rate and platelet adhesion and activation assays. The effects of the TS coating on the proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs) and the modulation of macrophage inflammatory function were assessed by in vitro cellular assays. The modulatory effect of the TS coating on macrophage phenotype was assessed using immunofluorescence staining. The antithrombotic effect of the coating was further explored by ex-vivo blood circulation assays. The successful preparation of TS-eluting stent was confirmed by WCA, FTIR, SEM and UV-Vis assays. The TS coating was able to maintain sustained release of TS in vitro for 28 d. The TS coating met the haemolysis rate requirement for biomedical implant materials. The in vitro cytocompatibility results showed that the TS eluting coating promoted the proliferation of ECs and inhibited the proliferation of SMCs, and could effectively regulate the inflammatory behavior of macrophages. Based on the in vitro biocompatibility results, a final concentration of 30% TS (mass ratio of TS to PLGA) was selected as the final application concentration. The results of the ex-vivo blood circulation experiments showed that the surface coating had a good inhibitory effect on thrombosis. In conclusion, the TS-eluting stent prepared herein has the ability to selectively promote endothelial proliferation, inhibit smooth muscle proliferation, modulate inflammation as well as excellent anti-thrombogenic ability, which can provide a potential solution for lesion vascular repair. |
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