基于“归经入脑”的天麻抗帕金森病的物质基础及机制研究

Gastrodia elata BL. is the genuine medicinal materials in Yunnan Province, and commonly used in the treatment of Parkinson’s disease(PD). Scholars consider that gastrodin is the material basis. However, the research group have found that the ethyl acetate extract(EAE) have the effect of anti-PD but excluding gastrodin, and the mechanism related to anti-oxidative stress. It is well known that drugs treat central nervous system diseases must achieve the therapeutic concentration through the blood-brain barrier(BBB). So, we hypothesized that Gastrodia related to the meridian tropism to brain. EAE targeting distribution in brain regions after oral administration, control gene expression of Nrf2-ARE oxidative stress pathway, and further lead to changes of brain function, structure and brain connections, to achieve the effect of anti-PD. The project will research on the effect of EAE on PD rats brain function, brain structure and connections by fMRI, the way and distribution of the active ingredients into the brain by opticalin vivo imaging, differentially expressed genes screened from Nrf2-ARE oxidative stress pathway by functional classification gene chip technique, protein expression of the differentially expressed genes verified by fluorescent immunohistochemistry technique, to clarify the material basis and mechanism of Gastrodia on anti-PD. The project will provide ideas on studying the theory of the meridian tropism and the development of new drugs of central nervous system.

天麻是云南省道地药材，常用于治疗帕金森病（PD）。有学者认为其抗PD的物质基础为天麻素。然而课题组研究发现，天麻乙酸乙酯萃取物（EAE）不含天麻素却具有明显抗PD作用，机制与抗氧化应激有关。众所周知，治疗中枢神经系统疾病的药物，通常需透过血脑屏障在脑部达到治疗浓度。因此，我们推测天麻可归经入脑，口服给药后EAE靶向分布于脑区，调控Nrf2-ARE氧化应激通路的基因表达，进一步导致脑功能、结构和脑连接的变化，产生抗PD的作用。为证实上述假说，本课题拟采用fMRI研究EAE对PD大鼠脑功能、结构和脑连接的影响，小动物活体成像技术研究有效成分入脑途径及分布，功能分类基因芯片筛选Nrf2-ARE氧化应激通路的差异表达基因，荧光免疫组化技术验证差异表达基因的蛋白表达，从而探讨天麻归经入脑治疗PD的现代科学内涵，阐明天麻抗PD的物质基础及机制。本课题将为归经理论的研究，为中枢系统类新药的研发提供思路。

天麻是云南省道地药材，临床常用于治疗帕金森病（PD）。有学者认为其抗PD的物质基础为天麻素。然而课题组研究发现，天麻乙酸乙酯萃取物（EAE）不含天麻素却具有明显抗PD作用，机制与抗氧化应激有关。众所周知，治疗中枢神经系统疾病的药物，通常需透过血脑屏障在脑部达到治疗浓度。因此，我们推测天麻可归经入脑，口服给药后EAE靶向分布于脑区，调控Nrf2-ARE氧化应激通路的基因表达，进一步导致脑功能和脑连接的变化，产生抗PD的作用。为证实上述假说，本课题采用fMRI研究了EAE对PD大鼠脑功能和脑连接的影响，LC-MS技术研究了EAE有效成分在脑内的代谢，小动物活体成像技术研究了有效成分在脑内的分布，功能分类基因芯片筛选了Nrf2-ARE氧化应激通路的差异表达基因，Western Blot技术研究了差异表达基因的蛋白表达，从而探讨了天麻归经入脑治疗PD的现代科学内涵，阐明了天麻抗PD的物质基础及机制。本课题为归经理论的研究，为中枢系统类新药的研发提供了思路。