基于“鼻通脑络"理论研究猪牙皂经鼻给药 "通关开窍"物质基础及作用机理

It was reported that Fructus Gleditsiae Abnormalis nasal powders is used to treat stroke, coma, excessive phlegm and syndrome of orifices confused by phlegm in Trad itional Chinese Medicine. Although Fructus Gleditsiae Abnormalis has a definite therapeutic effect , there is no report on the study of its efficacious material basis and mechanism of resuscitation. The result of the early experiment showed that the effective part of cerebral protection and expectorant effects of Fructus Gleditsiae Abnormalis, and plan to adopt mass spectrum analyses and preparative chromatography, combining with preparative chromatography ,cerebral microdialysis and the studies of PK-PD to analyze material basis of Fructus Gleditsiae Abnormalis on inducing resuscitation.On this basis, researching the action mechanism of Fructus Gleditsiae Abnormalis on inducing resuscitation by using modern molecular biology techniques. Based on the above research, the aim of study is to provide a powerful experimental theory for researching and producing available and high efficient nasal preparations of Fructus Gleditsiae Abnormalis , as well as a firm foundation for clinical application, and it has theoretical significance and significant guiding value in New Drug Research.

中医以猪牙皂制散吹鼻，治疗中风口噤，昏迷不醒，癫痫痰盛，关窍不通，疗效确切，但其物质基础及经鼻开窍机理尚无相关研究。本课题前期证明了猪牙皂具有明确的脑保护和祛痰有效部位，拟采用质谱分析定性和制备色谱分离，采用鼻腔给药和脑内微透析取样技术，通过PK-PD研究，分析猪牙皂“通关开窍”的物质基础；在此基础上，采用分子生物学现代科技手段，对猪牙皂经鼻给药“通关开窍”的作用机制进行研究，以此为研制治疗脑中风的速效、高效猪牙皂鼻用制剂提供有力的实验依据，也为猪牙皂鼻腔给药制剂的临床应用奠定坚实基础，具有重要的理论意义和新药研究指导价值。

中医以猪牙皂制散吹鼻，治疗中风口噤，昏迷不醒，癫痫痰盛，关窍不通，疗效确切，但其物质基础及经鼻开窍机理尚无相关研究。本课题前期证明了猪牙皂具有明确的脑保护和祛痰有效部位，现采用质谱分析定性和制备色谱分离猪牙皂皂苷部位，水蒸气蒸馏法对猪牙皂芳香类成分进行萃取及GC-MS确定各成分；以微透析取样技术、UPLC-MS/MS等分析测试技术，研究猪牙皂不同部位经鼻腔给药大鼠后入血入脑的情况，明确猪牙皂中芳香类和皂苷类成分是醒脑开窍的药效物质基础；在此基础上，采用分子生物学现代科技手段，Western blotting和免疫组化法检测检测各生理指标、病理指标，对猪牙皂经鼻给药“通关开窍”的作用机制进行研究，实验结果表明猪牙皂可能通过抑制缺血诱发的氧化损伤、调节血脂因子、减少炎症介质的产生，从而发挥神经保护作用；最后系统地研究了猪牙皂脂质体的制备工艺及其粘膜毒性的评价，将猪牙皂制成脂质体，以此起到增效减毒的作用，为猪牙皂探索一种新型鼻内给药系统，以此为研制治疗脑中风的速效、高效猪牙皂鼻用制剂提供有力的实验依据，也为猪牙皂鼻腔给药制剂的临床应用奠定坚实基础，具有重要的理论意义和新药研究指导价值。