人参皂苷Rg1通过抑制CKLF1调控小胶质细胞功能变化治疗脑中风的机制研究

中风病是导致我国居民死亡的首位病因，缺少有效治疗药物。气虚血瘀为该病基本病机，人参有大补元气之功，三七有化瘀止血之效，两者广泛用于中风病治疗，疗效确切。Rg1是人参、三七共有活性成分，抗中风效果显著，但药物靶点尚待阐明，限制了推广应用。CKLF1是我国科学家发现的趋化因子，可通过诱导小胶质细胞M1型极化反应，加重卒中后神经损伤。Rg1可抑制CKLF1诱导的小胶质细胞M1型极化，阻断CKLF1表达可抑制Rg1治疗中风的药理学功效。基于此，我们提出“Rg1通过抑制CKLF1调控小胶质细胞功能变化治疗脑中风”的科学假设。本项目拟以CKLF1基因敲除/过表达小鼠为研究对象，采用表面等离子共振、神经影像学、单细胞测序等技术，从分子、细胞和动物水平解析CKLF1在Rg1调控中风后小胶质细胞功能变化的生物学作用，为推动Rg1治疗脑卒中的临床应用提供理论基础。

Stroke is the leading cause of death for Chinese, and there is a lack of effective treatment. Qi deficiency of Qi and blood stasis are the basic pathogenesis of stroke in Chinese traditional medicine. Ginseng has the power of nourishing qi, and Panax notoginseng has the effect of removing blood stasis. Both of them are widely used in the treatment of stroke. Rg1 is a common active ingredient in panax ginseng and panax notoginseng, which has a significant anti-stroke effect, but its drug target has yet to be clarified, which limits its application. CKLF1 is a chemokine discovered by scientists in China, which can aggravate nerve injury after stroke by inducing M1 type polarizing reaction of microglia. Rg1 could inhibit CKLF1-induced microglial M1 type polarization, and blocking CKLF1 expression can inhibit Rg1's pharmacological efficacy in treating stroke. Based on this, we propose the scientific hypothesis that "Anti-stroke effect of Rg1 is by inhibiting CKLF1 mediated microglial function". This project intends to use CKLF1 gene knockout / overexpression mice as the research object, using surface plasmon resonance, neuroimaging, single cell RNA sequencing and other technologies to analyze the role of CKLF1 in the anti-stroke effect of Rg1 at the molecular, cellular and animal levels, which would provide a theoretical basis for promoting the clinical application of Rg1 in the treatment of stroke.