基于多靶向筛选策略和促NSC迁移新机制的民族药白脉散GEC治疗SN的药理学研究

Strok infarction neuropathy is called Baimai disease in China Mongolian medicine, which is a medical difficult problem. Promoting the migration of neural stem cell (NSC) plays an important role in the treatment, while there is no effective medicine as yet. Our previous research confirmed that the ancient Mongolian prescription Baimaisan is effective to treat cerebral infarction neuropathy by promoting NSC migration, while further study should help clarify the exact mechanism as well as the material basis of Baimaisan..In order to break through the conventional trace active ingredient separation technology, the applicant will adopt the mature target separation technology, and prepare new target screening materials base on the key target protein, such as c-kit and CXCR, which promote the migration of NSC, and capture target compounds targets. Establish NSC migration wound healing model to screen the compounds which can promote migration. Combine with UPLC-MSn to identify the components and obtain the group of effect compounds (GEC), which can promote NSC migration, as an candidate medicine for research. And then establish the NSC migration model in fluorescence and in vivo to study the migration activity. Synthetic studying the molecular mechanism of JAK/ERK in GEC from the whole, molecular and gene level, and focused on the genetic change, target level and molecular network mechanism of the key genes STAT and MAPK signaling pathway. Clarify the scientific basis and advantages of Baimaisan to regulate migration, and the outcome has scientific value and application prospect.

脑卒中神经病变(SN)是医学难题，属蒙医白脉病范畴。基于神经营养、神经干细胞(NSC)移植策略的药物和疗法效果不理想，研究新机制创新药物意义重大。已结题面上项目取得进展，发现蒙药经典方剂白脉散促NSC迁移治疗SN活性好，属新机制，亟待研究，但发现微量活性成分分离时丢失。拟发挥交叉技术优势，制备3种新型靶向分离材料，建立灵敏特异的多靶向筛选体系捕获微量活性成分，并利用体外迁移模型筛选促迁移活性成分，以获得有效成分组GEC。进而建立4种NSC迁移模型在体内体外系统研究GEC的活性和药理机制，综合分析GEC促NSC迁移的JAK/MAPK分子网络及关键节点基因表达。课题构建的多靶向筛选体系有推广价值，获得的新机制GEC和新活性化合物极具应用前景，成果有助于理解蒙药白脉散促NSC迁移抗SN的科学基础和多靶点优势，也为获得源于民族药、高于民族药的创新药物提供关键技术资料，课题具有科学价值和应用前景。

在国家自然科学基金委的大力资助下，课题组针对民族医药和民族地区重大需求开展攻关研究。脑卒中神经病变（Stroke neuropathy，SN）是临床医学难题，可导致患者偏瘫、失语、致残，甚至死亡。脑卒中神经病变在蒙医学和藏医学属于白脉病范畴，是青藏高原和蒙古草原广大居民的常见病和高发病，历史上积累的丰富临床经验具有重要科学价值，亟待挖掘整理。.课题组按申请书内容认真实施，超额完成任务和成果。并创造性开展工作，建立了靶向筛选技术从白脉散中富集、垂钓常规技术丢失的活性化合物，确定活性成分群，进而利用划线迁移筛选活性化合物，利用Transwell迁移模型和划线迁移模型研究GEC的促迁移活性。建立多个动物模型和细胞模型，评价获得的候选药物。重点阐明SDF-1α、CXCR4和MAPK通路下游信号（ERK1/2、p38和JNK）的变化情况，已取得18项结果（已标注基金号）。发表12篇高水平论文，其中包括Top期刊论文2篇（中科院大类一区）、中科院大类二区论文多篇。本课题的成果获得省部政府科技奖和各类高水平科技奖励4项，其中包括省部级政府颁发的科技进步二等奖1项，全国一级行业协会科技进步一等奖2项、二等奖1项。专利成果向西藏、内蒙等民族地区转化成功2项，取得了良好的社会效益和经济效益，不仅保证了基金委在推动基础科学研究方面的投入绩效，也实现了基金委提倡的科技成果转化应用方面的目标。