原位催化生成NO的人工血管材料炎症反应调控及其对血管再生行为的影响

In addition to anti-thrombotic property and rapid endothelialization, the key factors for successful transplantation of small-diameter artificial blood vessels include promotion of smooth muscle cell infiltration, absence of restenosis induced by intimal hyperplasia, remodeling of extracellular matrix and prevention of calcification. Nitric oxide (NO) not only reduces coagulation and promotes the proliferation of endothelial cells, but also plays a key role in vascular biology due to its regulation of inflammatory response after vascular graft implantation. This project will focus on how in situ catalytic NO generation of artificial blood vessels controls the inflammatory reaction and affects macrophage polarization, and then influence the behavior of vascular smooth muscle cells, and eventually participate in angiogenesis and vascular remodeling. Through cellular experiment, subcutaneous implantation and in situ transplantation experiment, this project will investigate phenotype switch of macrophage and expression of related protein, and then probe the specific mechanism through which NO influences macrophage polarization and regulates inflammation by using immunocytochemistry, Western Blot, and RT-PCR. Through evaluating the proliferation and migration of vascular smooth muscle cells and structural and functional regeneration of artificial blood vessels, we aim at figuring out the mechanism by which inflammation response, especially macrophage polarization, affects vascular regeneration process. We hope to realize intentional control of vascular cell phenotype by regulating the phenotype of macrophages, and then promote tissular and functional regeneration of artificial blood vessels. So, this project has great scientific significance and application value.

小口径人工血管移植成功的关键因素除了抗急性血栓和快速内皮化之外，还在于能促进血管平滑肌细胞浸润、无内膜增生性再狭窄、促进细胞外基质重塑和无钙化现象。一氧化氮不仅能抗凝血和促进内皮细胞增殖，还因参与调控炎症反应，在血管生物学中起重要作用。本研究重点考察原位催化生成一氧化氮的人工血管材料如何调控炎症反应，影响巨噬细胞极化，进而影响血管平滑肌细胞的行为，并最终在血管再生与重塑中发挥作用。通过细胞实验、皮下埋植和原位移植实验，利用免疫荧光染色，Western Blot以及RT-PCR技术，深入考察该血管材料巨噬细胞极化以及相关蛋白表达，研究影响巨噬细胞极化分型和调控炎症反应的机制；通过评价平滑肌细胞增殖迁移、血管结构和功能再生，认识炎症反应（尤其是巨噬细胞极化）在人工血管再生过程中的作用机制，以期通过调控巨噬细胞表型，主动调控血管细胞行为，促进血管组织与功能再生。因此具有重要的科学意义和应用价值。

小口径人工血管移植成功的关键因素除了抗急性血栓和快速内皮化之外，还在于能促进血管平滑肌细胞浸润、无内膜增生性再狭窄、促进细胞外基质重塑和无钙化现象。一氧化氮不仅能抗凝血和促进内皮细胞增殖，还因参与调控炎症反应，在血管生物学中起重要作用。本研究重点考察原位催化生成一氧化氮的人工血管材料如何调控炎症反应，影响巨噬细胞极化，进而影响血管平滑肌细胞的行为，并最终在血管再生与重塑中发挥作用。通过细胞实验、皮下埋植和原位移植实验，利用免疫荧光染色Western Blot以及RT-PCR技术，考察了血管材料巨噬细胞极化以及相关蛋白表达，研究影响巨噬细胞极化分型和调控炎症反应的机制； 通过调控人工血管植入后的炎症反应，诱导巨噬细胞向促进再生的M2表型转化，进而诱导vSMC在人工血管中层维持收缩表型，抑制其向人工血管内壁的过度迁移，促进人工血管壁的毛细血管化，增强血管功能。初步阐述了一氧化氮影响巨噬细胞极化分型和调控炎症反应的机制；认识炎症反应（特别是巨噬细胞极化）对血管细胞行为的影响，阐述了炎症反应调控在血管再生过程中的作用机制。.项目建立了7个小口径人工血管设计构建和功能评价新体系。所取得的研究成果具有创新性，通过层层组装技术，负载含硒催化剂有机硒修饰的聚乙烯亚胺，构建可催化生成并缓释一氧化氮（NO）的小口径人工血管等技术方法具有自主知识产权。.项目已申请国家发明专利4项，授权发明专利2项；发表相关学术论文13篇（其中，SCI收录论文7篇；国内核心期刊论文6篇）；参与壮大了血管组织工程研发团队；培养了位4位博士毕业生和3位硕士毕业生；一项人工血管授权专利技术实现转让；所取得的成果对于未来形成新的经济增长点和改善人类健康状况意义重大，具有较好的社会、经济效益。