基于神经保护作用的栝楼桂枝汤药效物质及配伍机理研究

经方栝楼桂枝汤临床上用于脑卒中后康复有独特疗效，为了阐明栝楼桂枝汤神经保护的药效物质及其配伍机理，本研究从体内外两方面进行研究，首先，拟采用HPLC-DAD-Q-TOF-MS/MS和UPLC-QqQ-MS/MS联用技术，定性与定量探讨复方君、臣、佐、使不同配伍模式下物质基础的变化，结合细胞微电子阻抗技术实时监测分析不同配伍模式下复方对兴奋性毒性/氧化应激损伤神经保护作用的差异，通过“质”、“量”、“药效”相结合分析栝楼桂枝汤神经保护作用的药效物质及体外配伍机理。其次，拟采用MD-2DLC-Q-TOF/MS联用技术，定性分析栝楼桂枝汤配伍前后大脑中动脉阻塞MCAO模型大鼠复方体内血清/脑脊液药物化学组分，阐明复方血/脑中神经保护的移行成分；并在此基础上，选择活性标志物成分，采用UPLC-QqQ-MS/MS技术分析神经保护移行成分配伍前后药代动力学参数的变化，阐明复方药效物质体内配伍机理。

The famous preparation gualou-guizhi decotion(GLGZD) is good for the recovery of illness after stroke happening in clinical practice. In order to illustrate the material foundation of neuroprotection and their mechanism of compatibility, our research intends to study it from both in vivo and in vitro models. Firstly, a qualitative analytical method of HPLC-DAD-Q-TOF-MS/MS was developed for identification of multi-constituents and an UPLC-QqQ-MS/MS analytical method was developed for simultaneously determining multi-constituents in GLGZD and its different herbal fomulation compatibility groups, and then all groups’ neuroprotective cause by excitatory toxicity of glutamate or oxidative stress were further evaluated by cell microelectronics impedance technology. As a result, studing the material foundation of neuroprotection and their mechanism of compatibility in vitro is by combining above-mentioned qualitative, quantitative and neuroprotective results. Secondly, a MD-2DLC-Q-TOF/MS method was developed for researching pharmacochemistry and cerebrospinal fluid-chemistry in MCAO model rat. On this foundation, an UPLC-QqQ-MS/MS analytical method was developed to determining active marker in GLGZD and further applied to pharmacokinetics after oral administration to rats. The changes of different pharmacokinetic parameters between GLGZD and its ingredient herbals were studied and would further illustrate the material foundation of neuroprotection and their mechanism of compatibility in vivo.