用于二尖瓣关闭不全的新型二尖瓣瓣膜支架的实验研究

The principal treatment for severe mitral regurgitation (MR) is mitral valve replacement or repair under cardiopulmonary bypass,but it is judged highrisk and big traumas.Encouraged by the positive experience with transcatheter aortic valve replacement,transcatheter mitralt valve implantation(TMVI) is desired by clinical treatment.It is also the research hotspot in cardiovascular field. For minimally invasive and off pump,TMVI is suitable for high-risk or inoperable patients. A number of research groups are currently engaged in the development of TMVI. Severe technical challenges have been encountered in the application of this approach in animal and few clinical experiment, especially in effective fixing, perivalvular leakage, surgical technic and so on. Based on our previous study,we have manufactured a new-type mitral valved stent which be fixed by a variety of ways, reduced perivalvular leakage with several ways and released through multi-stage segmental model. Excellent performances of the valved stent have been showed through preliminary experiments in vivo and in vitro. In this study we aim to improve new-type mitral valved stent, delivery system and test system, to optimize parameter selection, to evaluate its performances in vitro, and its feasibility, safety and effect by implanting it in pigs.We also attempt to establish perfect surgical techniques and methods.

严重二尖瓣关闭不全患者首选行体外循环下二尖瓣修补或置换手术，但创伤大、风险高。随着经导管主动脉瓣膜置换技术的成功应用，经导管二尖瓣瓣膜置换技术成为目前临床的迫切需要及研究热点，主要优势为微创、无需体外循环，尤其适用于无法耐受常规手术的危重病人。近年来国际上已有几种在研的二尖瓣瓣膜支架，经动物及少量的临床研究显示，在支架体内固定、瓣周漏、手术技术等方面仍存在障碍。本课题组在既往瓣膜支架研究的基础上，设计研制了一种采用多种方式固定、多途径防止瓣周漏及多级分段释放模式的新型二尖瓣瓣膜支架，通过初步的体内外实验表明该瓣膜支架各项性能优良。本研究拟改进和优化该新型二尖瓣瓣膜支架、输送系统及体外瓣膜支架测试系统，通过系统的体内外实验研究，优化参数选择，明确新型二尖瓣瓣膜支架体外各项性能及在大动物体内行经导管二尖瓣置换的可行性、疗效及安全性，并建立一套完善的手术技术和方法。

二尖瓣关闭不全 (MR)是最常见的心脏瓣膜疾病，发病率和死亡率较高。严重MR患者的标准手术治疗是体外循环下行瓣膜修复或置换。虽然手术瓣膜修补或置换的技术成熟，疗效确切，但三分之一的严重MR患者存在手术治疗死亡的风险。近年来经导管二尖瓣瓣膜置换术（Transcatheter Mitral Valve Implantation，TMVI）逐渐发展起来，具有创伤小、手术时间短、不需要体外循环等优点，但是该技术仍不成熟。本项目成功研制了一种新型的经导管二尖瓣瓣膜支架系统，在瓣膜内固定、瓣周漏和瓣膜释放等方面具有多项创新，克服TMVI存在的障碍。通过体外研究、流体力学等多项体外实验，验证其流体力学性能，并通过大动物体内初步的TMVI术实验，验证其经导管二尖瓣置换的可行性，并建立了一套完善的TMVI手术技术和方法，有望进行临床转化，提供更为微创的瓣膜置换技术和装置。通过基础研究实验表明抑制miR-92a对低氧或高糖诱导的内皮祖细胞损伤有保护作用，MiR-92a通过调节GDF11及其下游的Smad2/3/FAK/Akt/eNOS信号通路介导影响内皮祖细胞的功能，该机制为促进支架内皮化、减少术后血栓提供了思路。本项目获得省部级奖励1项，发表SCI论文4篇，培养硕士研究生2名，培养博士研究生2名，获授权国家发明专利1项，授权实用新型专利2项，申请国家发明专利1项。