基于TWEAK-Fn14介导脑-心轴研究银杏叶提取物治疗缺血性中风诱发脑心综合征的作用机制

缺血性中风诱发的脑心综合征严重增加了患者的致死率和经济负担，且缺乏有效的治疗药物和靶点。前期研究发现，中风后小鼠脑中TWEAK含量与心脏LVEF呈负相关，且心肌组织Fn14基因显著上调；银杏叶提取物通过降低TWEAK的分泌，Fn14蛋白的表达，调节TWEAK-Fn14分别抗脑缺血损伤和心肌缺血损伤。因此，我们提出“银杏叶提取物调节TWEAK-Fn14介导脑-心轴治疗缺血性中风诱发脑心综合征”的科学假说。通过脑心综合征动物和细胞效应平台，应用注射重组TWEAK蛋白、Fn14基因敲除小鼠、Fn14蛋白抑制剂等手段，研究银杏叶提取物影响TWEAK-Fn14及其下游分子，改善缺血性中风诱发的心功能紊乱和心肌损伤。揭示TWEAK-Fn14介导脑-心轴为银杏叶提取物治疗缺血性中风诱发脑心综合征的科学内涵，为治疗脑心综合征的药物和靶点研究提供新的视角和科学依据。

Ischemic stroke complicated with brain-heart syndrome exacerbates the mortality and disability seriously. At present, there is still lack of definite understanding of its therapeutic targets and drugs. The previous study of us found that Fn14 gene in the myocardium is significantly up-regulated in the myocardium after stroke in mice, and the TWEAK content in the brain is negatively correlated with LVEF of heart. Ginkgo biloba extract can protect against myocardial ischemia injury and cerebral ischemia injury by regulating TWEAK-Fn14. Accordingly, we propose the scientific hypothesis that Ginkgo biloba extract regulates TWEAK-Fn14-mediated brain-heart axis to treat ischemic stroke-induced brain-heart syndrome. Through the platform of brain-heart syndrome animal and cell model, and with the help of injection of recombinant TWEAK protein, Fn14 knockout mice, Fn14 protein inhibitor and other methods, we aim to study the effect of Ginkgo biloba extract on TWEAK-Fn14 and its downstream molecules, so that to improve ischemic stroke-induced cardiac dysfunction and myocardial damage. It reveals that TWEAK-Fn14-mediated brain-heart axis is the scientific connotation of Ginkgo biloba extract in the treatment of brain-heart syndrome induced by ischemic stroke, and provides a new perspective and scientific basis for the study of drugs and targets for the treatment of brain-heart syndrome.