脑卒中作为世界第二大致死性疾病，发病率高临床预后差。神经炎症贯穿卒中的整个病理过程，是影响卒中后组织修复的关键因素，深入研究其分子机制并开发临床有效的药物至关重要。申请人发现线粒体分裂参与调节小胶质细胞极化过程，祛痰中药天南星的活性成分-夏佛塔苷在体外能通过上述机制减轻神经炎症，并筛选出可能介导其活性的关键分子lncRNA Ens6。提出假说：夏佛塔苷通过抑制lncRNA Ens6表达，降低线粒体分裂水平，促进M2小胶质细胞极化，改善缺血再灌注损伤。拟在动物和细胞水平上借助转录组测序、转基因小鼠构建等多种手段评价夏佛塔苷抑制线粒体分裂促进M2小胶质细胞极化改善缺血再灌注损伤的作用；阐明lncRNA Ens6介导夏佛塔苷抗脑卒中活性的分子机制。为夏佛塔苷及天南星防治缺血性脑卒中的临床应用提供实验依据，为脑卒中的药物开发提供新的潜在作用靶标，为阐释从“痰”论治中风的科学内涵积累数据。

Stroke is the second leading cause of death in the world with a high incidence rate and poor clinical prognosis. Neuroinflammation runs through the whole pathological process of stroke and is a key factor affecting tissue repair after stroke. Therefore, a deep understanding of the molecular mechanism behind neuroinflammation and development of clinically effective drugs are of vital importance. We discovered that schaftoside, an active ingredient of the Chinese herbal medicine Arisaema heterophyllum Blume, is capable of inhibiting mitochondrial fission, regulating microglial polarization and reducing neuroinflammation. And lncRNA Ens6 was identified as the key molecule for schaftoside to mediating its activity. We hypothesize that lncRNA Ens6 facilitate schaftoside in the inhibition of mitochondrial fission, M2 microglial polarization and the improvement of ischemia-reperfusion injury. We plan to utilize a CRISPR knock-in mouse model, global transcriptome sequencing, and other molecular approaches to evaluate the effects of schaftoside on inhibiting mitochondrial fission, promoting M2 microglia polarization and improving ischemia-reperfusion injury. And to elucidate the function of lncRNA Ens6 in mediating the activity of schaftoside in improving ischemia-reperfusion injury. Our results will provide the experimental basis for the clinical development and application of schaftoside in the prevention and treatment of ischemic stroke. Findings will also provide a new potential target for the development of new drugs for stroke, and accumulate data for the explanation of the scientific connotation of treating stroke from "Tan".