【作者】 张宁一；

【导师】 周春祥；

【作者基本信息】 南京中医药大学 ， 中医临床基础， 2009， 博士

【摘要】 本课题从理论研究和实验研究两方面入手,基于“卫气根于肾”理论,对温肾补阳法的理论基础、效用机制及其干预造血干细胞向免疫细胞分化的可能性作了初步探索。鉴于现代医学中人体防御机制与中医卫气部分功能的相似性,理论研究部分重新论述和界定了传统中医学理论中“卫气”、“肾”等与现代免疫学机制相关的概念,认为“卫气根于肾”实质是对卫气和肾之间关系的描述,而并非对其余各脏腑在卫气起效过程中作用的否定;在将“卫阳不足”的病因病理概括为内伤于肾和外伤于邪两个方面的基础上,提出温肾能从质和量两个方面增强卫气,从而起到“助卫阳”的作用,是治疗的关键。在此中医理论基础上,结合造血干细胞及免疫细胞相关知识,提出促进造血干细胞向免疫细胞分化可作为温肾补阳作用物质基础的构想。结合《内经》、《伤寒论》有关理论及历代医家相关见解,对卫阳不足证特别是桂枝加附子汤证病机进行分析,选用中药附子为温肾补阳代表药物,依据现代医学对造血干细胞在免疫体系中所起作用的认识,以卫气与免疫相关性为结合点,对附子的温肾补阳效用及其可能机制作了初步分析推断。实验研究首先在环磷酰胺小鼠免疫抑制模型基础上,对附子对抗免疫抑制状态的效用及其对提高生活质量(主要指标为体重和食量)和延长生存时长的作用作了评估,结果显示附子能对抗小鼠免疫抑制状态,附子组在生存质量和生存时间上较模型组有显著提高(P＜0.05),相关效用与附子药液浓度有一定的关联,其中以高剂量组效果较显著。其次,通过解剖检测胸腺指数和脾脏指数,观察温肾补阳法对免疫的影响。结果显示,胸腺指数在高、低剂量附子的干预下都与模型组和空白组有差异(P＜0.05),中剂量下无显著差异;脾脏指数在附子的干预下与模型组比减小,其中高、低剂量下差异显著(P＜0.05),在证实温肾补阳药物可能对免疫有一定影响的基础上,认为附子的作用大小可能与其剂量有关,且其关键作用机制也可能随剂量大小而有所改变。本课题还通过检测外周血中小鼠树突状细胞特异性表面标志33D1和小鼠造血干细胞特异性表面标志Sca-1的表达情况,对温肾补阳药物可能的作用环节作了初步探索。结果显示,外周血DC Marker(33D1)和Sca-1表达在不同剂量附子干预下并无显著差异(P＞0.05),但实验数据与附子药量表现出一定的量效关系。为进一步探索其中的效用机制,可能尚需在此结果上,围绕干细胞分化方向、皮肤粘膜免疫功能与卫气的相关性等一系列问题,作进一步的实验研究。更多还原

【Abstract】 Based on related theories and laboratorial researches, the foundational theories of "defensive qi rooted in kidney" and the functions and mechanism of "warm kidney to activate yang" are discussed.In view of the similarity of the function of defense mechanism in modern medicine and "defensive qi" in traditional Chinese medicine, the following theories about "defensive qi rooted in kidney" which are relevant to modern immunologic mechanisms such as "defensive qi", "warm kidney to activate yang", "kidney", and so on are introduced to demonstrate the etiology and pathology of "the lack of defensive qi" and elaborate the essence of "defensive qi rooted in kidney".Besides, by means of discussing syndrome of decoction GUI ZHI(Ramulus cinnamomi)JIA FUZI, combining with Shang Han Lun and comments of previous experts, the notion that hematopoietic stem cells (HSCs)is one of the substantial foundation of "kidney" in the process of "warm kidney to activate yang" is putting forward.On the basis of the theories above and related researches made by other doctors, the idea that warming kidney works by activating HSCs to differentiate into antigen presenting cells (APCs) is proposed. On the overall level, model of immune suppression is used to research and evaluate the function of FUZI. The conclusion is that FUZI may improve the living standards, prolong the lifespan and oppose to Cyclophosphamide.In addition, a further research is made to find out the secret how FUZI works by using HSCs and dendritic cells which have been proved to be the most important APCs. In the process, some modern theories and experimental methods like flow cytometry are used. The results show that the DC Marker and Sca-1 may be effected by FUZI, but no statistical significant between-group differences have been found. To explore the mechanisms in this course of event, some further considerations are necessary. Focus on the differentiation direction of stem cells, the immune function in skin and mucous membranes may be able to help.更多还原