抗脑缺血/再灌注损伤新靶点：脑IDOL-LDLR轴及硫化氢干预机制的研究

It is of great significance to further explore new target for of cerebral ischemia/ reperfusion injury (CI/RI) for the prevention and treatment of Ischemic stroke (IS). Studies have demonstrated that cholesterol metabolism is closely related to Ischemic stroke. IDOL-LDLR axis is a novel important regulation way of cholesterol metabolism and IDOL can negatively regulate the expression of LDLR. Our preliminary experiment found that there were upregulation of IDOL and downregulation of LDLR in the brain of cerebral ischemia / reperfusion injury mice. We hypothesize that the IDOL-LDLR axis is a new target for the treatment of CI / RI. This project is planned in the CI / RI patients and mice to clarify the role of IDOL-LDLR axis in the pathogenesis and treatment of CI / RI by analyzing the changes of IDOL and LDLR expression in the brain and exploring the effects of changes in the brain IDOL-LDLR axis, using gene transfection and RNA interference. On this basis, we will explore further the function and mechanism of anti-CI / RI action of H2S. This project will reveal a new target for prevention and treatment of CI / RI, elucidate the mechanism underlying the anti-CI / RI effect of H2S, to provide new targets for prevention and treatment of IS and to expand new ideas for the development of clinical drugs of IS from the new perspective of IDOL-LDLR axis.

深入探讨防治脑缺血/再灌注损伤（CI/RI）的新靶点对防治缺血性卒中（IS）具有重要意义。研究表明，胆固醇代谢与缺血性卒中密切相关。IDOL-LDLR轴是新发现的胆固醇代谢重要调节途径，IDOL可负调节LDLR的表达。预实验发现脑缺血/再灌注损伤鼠脑内高表达IDOL和低表达LDLR。我们推测：IDOL-LDLR轴是防治CI/RI的新靶点。本课题将在CI/RI患者和CI/RI鼠上，分析脑IDOL-LDLR轴的变化；利用基因转染和RNA干扰技术，改变脑内IDOL-LDLR轴对CI/RI的影响，以明确IDOL-LDLR轴是CI/RI的新靶点。在此基础上，探讨H2S抗CI/RI作用及机制。本项目将从脑IDOL-LDLR轴这一新视角揭示防治CI/RI的新靶点和阐明H2S的抗CI/RI作用机制，为防治IS提供新靶点，为其临床药物的研发拓展新思路。

深入探讨防治脑缺血/再灌注损伤（CI/RI）的新靶点对防治缺血性卒中（IS）具有重要意义。研究表明，胆固醇代谢与缺血性卒中密切相关。IDOL-LDLR轴是新发现的胆固醇代谢重要调节途径，IDOL可负调节LDLR的表达。预实验发现脑缺血/再灌注损伤鼠脑内高表达IDOL和低表达LDLR。我们推测：IDOL-LDLR轴是防治CI/RI的新靶点。本课题将在CI/RI患者和CI/RI鼠上，分析脑IDOL-LDLR轴的变化；利用基因转染和RNA干扰技术，改变脑内IDOL-LDLR轴对CI/RI的影响，以明确IDOL-LDLR轴是CI/RI的新靶点。在此基础上，探讨H2S抗CI/RI作用及机制。本项目将从脑IDOL-LDLR轴这一新视角揭示防治CI/RI的新靶点和阐明H2S的抗CI/RI作用机制，为防治IS提供新靶点，为其临床药物的研发拓展新思路。