中文摘要
深入探索H2S发挥心血管效应的细胞与分子机制，取得了突破性进展。揭示H2S心血管舒张效应的离子通道调节机制包括促进VSMC中KATP通道表达及抑制心肌细胞L型钙通道开放，并将其作用靶点确定于L型钙通道的巯基；发现MAPK 和NF-κB 信号途径介导H2S对VSMC增殖、凋亡和胶原重塑的调节作用；揭示H2S可通过直接清除自由基、线粒体保护等机制发挥抗氧化应激和抗内质网应激的心血管保护作用；发现NF-κB 信号途径介导H2S的抗血管炎症效应，在血管损伤性疾病中发挥重要保护作用。在此基础上，揭示另一种气体分子二氧化硫（SO2）在心血管系统存在生成体系，并对其心血管调节作用进行了探索，发现并提出SO2是心血管调节的又一新型气体信号分子。在课题执行期间，围绕上述研究内容，在Arterioscler Thromb Vasc Biol、Antioxid Redox Signal等杂志上发表论文73篇，其中SCI论文24篇。主办首届以及第2届全国气体信号分子硫化氢暨血管活性肽研究进展报告会（2007和2010）及第5届中韩日小儿心脏心脏论坛（2009）。培养长江学者特聘教授1名，北京市科技新星1名。
英文摘要
The investigators explored the cellular and molecular mechanisms of the regulatory effects of hydrogen sulfide (H2S) on cardiovascular system and made great progress. It was discovered that the mechanisms for its cardiovascular relaxant effects involved upregulating the expression of KATP channel subunits in vascular smooth muscle cells and inhibiting L-type calcium channels in myocardial cells. And the thiol groups in α subunits of L-type calcium channels were found to be the targets of negative inotropic function for H2S. MAPK signaling pathway and NF-κB signaling pathway mediated the effects of H2S on vascular smooth muscle cell proliferation, apoptosis and collagen remodeling. H2S exerted antioxidative effects and anti-ERS effects via directly getting free of free redicals and protecting mitochondria injury. It was discovered that NF-κB signaling pathway mediated H2S anti-inflammatory effects in vessels, which played an important role in the development of vascular injury diseases including arthrosclerosis, pulmonary hypertension and systemic hypertension. Forthermore, the investigators showed in the metabolism of sulfur-containing amino acids, another gaseous molecule sulfur dioxide (SO2) had its endogenous generating pathway and discovered that SO2 was another novel gasotransmitter in cardiovascular system
结题摘要
深入探索H2S发挥心血管效应的细胞与分子机制，取得了突破性进展。揭示H2S心血管舒张效应的离子通道调节机制包括促进VSMC中KATP通道表达及抑制心肌细胞L型钙通道开放，并将其作用靶点确定于L型钙通道的巯基；发现MAPK 和NF-κB 信号途径介导H2S对VSMC增殖、凋亡和胶原重塑的调节作用；揭示H2S可通过直接清除自由基、线粒体保护等机制发挥抗氧化应激和抗内质网应激的心血管保护作用；发现NF-κB 信号途径介导H2S的抗血管炎症效应，在血管损伤性疾病中发挥重要保护作用。在此基础上，揭示另一种气体分子二氧化硫（SO2）在心血管系统存在生成体系，并对其心血管调节作用进行了探索，发现并提出SO2是心血管调节的又一新型气体信号分子。在课题执行期间，围绕上述研究内容，在Arterioscler Thromb Vasc Biol、Antioxid Redox Signal等杂志上发表论文73篇，其中SCI论文24篇。主办首届以及第2届全国气体信号分子硫化氢暨血管活性肽研究进展报告会（2007和2010）及第5届中韩日小儿心脏心脏论坛（2009）。培养长江学者特聘教授1名，北京市科技新星1名。