基于“肝肾相关”理论从Ca2+-CaM/CaMKⅡ-CREB信号转导途径探析黑逍遥散防治阿尔茨海默病的可行性

Feasibility of Hei Xiaoyaosan in Preventing and Treating Alzheimer’s Disease Based on Theory of ’Correlation of Liver and Kidney’ Based on Ca-CaM/CaMKⅡ-CREB Signal Pathway

阿尔茨海默病(AD)是一种起病隐匿的增龄性神经退化性疾病,随着社会老龄化发展趋势而迅猛增加,严重威胁着人民群众健康,如果缺乏有效防治措施,将给社会经济和医疗保障体系造成巨大冲击。研究发现细胞信号转导异常是许多疾病发生的关键环节,细胞信号转导理论被广泛应用于阐明中医脏象实质和中医药作用机制的研究。"肝肾相关"是"五脏相关"理论的核心板块之一,适用于复杂疾病发病机制的阐释,解释多证候的相关性,及指导临证处方用药。黑逍遥散作为本研究组基于肝肾相关理论防治AD的首选复方,可通过疏肝养血、健脾益肾,通脑络利神窍而发挥防治AD作用。本文基于"肝肾相关"理论,从中医学角度阐述了AD的发病机制,通过查阅文献并结合前期研究,提出了从Ca2+-钙/钙调蛋白依赖性蛋白(CaM)/钙/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)-环磷酸腺苷反应元件结合蛋白(CREB)细胞信号转导途径防治AD的方法与思路。

Alzheimer’s disease(AD)is an incipient aging neurodegenerative disease,which increases rapidly along with the development trend of social aging and seriously threatens the health of the people. In the absence of effective preventive measures,it will have an enormous impact on the socio-economic and healthcare system. The study found that abnormal cell signal transduction is a key link in many diseases. Cell signal transduction theory has been widely used to clarify the essence of traditional Chinese medicine visceral image and the mechanism of traditional Chinese medicine. ’Correlation of Liver and Kidney’ is one of the core plates of the theory of ’Correlation of Five Organs’,which is suitable for explaining the pathogenesis of complex diseases and the correlation of multiple syndromes,and guiding the prescription of clinical syndrome. Hei Xiaoyaosan,as the first choice compound for the prevention and treatment of AD based on the theory of "Correlation of Liver and Kidney’ in our team,can play the effects of prevention and treatment by soothing liver and nourishing blood,strengthening spleen and tonifying kidney,and promoting brain collaterals and dredging viscerab spirit.Based on the theory of ’Correlation of Liver and Kidney’,this paper expounds the pathogenesis of AD from the perspective of traditional Chinese medicine,and puts forward the methods and ideas of the preventing and treating of AD from Ca2+-calcium/calmodulin dependent protein(CaM)/calcium/calmodulin dependent protein kinase Ⅱ(CaMKⅡ)-cyclic adenosine phosphate reactive element binding protein(CREB) cell signal transduction pathway by consulting literatures and previous studies.