基于荧光探针技术的中药紫红獐牙菜GSTs抑制剂快速筛选研究

如何实现中药活性成分快速筛选是中药新药开发及中药现代化研究的重要科学问题。荧光探针能快速、灵敏、特异性地识别靶标，实时监测和跟踪目标物，有望成为中药活性成分快速筛选的有用工具。本课题聚焦于肿瘤耐药及治疗的关键靶标谷胱甘肽巯基转移酶（GSTs），借助GSTs靶向荧光探针建立中药活性成分快速筛选方法，寻找“肝炎草”紫红獐牙菜中GSTs抑制成分。根据药效成分引起GSTs活性变化的荧光可视化实时监测过程，挖掘药效成分——GSTs活性——荧光响应值关系轴的变化规律，快速捕捉GSTs活性抑制成分。融合细胞成像、GSTs表达检测、计算机模拟分子对接等现代生化技术，辅以逆转肝肿瘤顺铂耐药等药理研究多角度验证筛选方法的可靠性。本课题首次采用荧光探针技术建立中药紫红獐牙菜GSTs抑制剂快速筛选平台，旨为构建中药活性成分快速筛选方法提供新思路。

The rapid screening of active ingredients of traditional Chinese medicine (TCM) is a significant topic of scientific research on developing new TCM drugs and TCM modernization. Fluorescent probes thus developed for sensitive and rapid identification of targets and for real-time monitoring of active TCM ingredients possess the potential to screen active TCM ingredients.This research centers on glutathione S-transferase (GSTs), a key target for tumor drug resistance and tumor treatment. A rapid screening method will be developed to identify active TCM ingredients aiming to find GSTs inhibiting components from Swertia punicea Hemsl. Real-time visual monitoring of pharmacodynamic components induced fluorescence change in GSTs activity can reveal relationship between pharmacodynamic components, GSTs activity and value of fluorescence response that renders a rapid capture of active GSTs inhibiting components. This screening method can be validated by up-to-date biochemical techniques such as cell imaging, GSTs detection and computer simulation of molecular docking. Also, its reliability can be further established through pharmacological studies on reversing drug resistance of cisplatin.This study first-ever employs fluorescent probe technology to develop a screening platform for rapid seperation of GSTs inhibitors from Swertia punicea Hemsl. It aims to open a new gateway to rapid screening of active TCM ingredients.