基于整体代谢网络的血瘀证“异病同证”（冠心病、糖尿病）的生物学基础研究

Blood stasis syndrome is one of the most common clinical syndromes of coronary heart disease (CHD) and diabetes. “Different diseases with the same syndrome” is the basic characteristics of the syndrome differentiation and treatment in traditional Chinese Medicine (TCM). According to the “Common Soil theory”, there may be some common pathological mechanism in the both of CHD and diabetes, that is “Common Soil”. The biological basis of blood stasis syndrome of “different disease (CHD, diabetes) with the same syndrome” may be closely related to the common pathological mechanism of CHD and diabetes. In our previous study, we have confirmed potential biomarker of blood stasis syndrome of CHD with the method of 1HNMR and so on, which partly reveal the biological basis of blood stasis syndrome. In this study, we plan to base on different diseases with the same syndrome and common soil theory, collecting blood stasis syndrome of CHD and diabetes patients as study objects, using metabonomics technique to explore the biological foundation of blood stasis syndrome, which is meaningful for clinical diagnosis of blood stasis syndrome. Study one: we plan to use 1HNMR technique based on principle and method of systems biology, to explore the potential biomarkers and abnormal global metabolic pathways of blood stasis syndrome of “different disease with the same syndrome”, and illuminate the biological foundation of blood stasis syndrome. Study two: by analyzing the association among potential biomarkers of blood stasis syndrome of “different diseases with the same syndrome”, TCM syndrome information of blood stasis and biochemical results, the study is to explore the syndrome essence of blood stasis syndrome.

血瘀证是冠心病和糖尿病最常见的临床证候之一，“异病同证”是中医辨证论治的基本特征。“共同土壤学说”认为：冠心病、糖尿病具有某些共同的病理机制，即“共同的土壤”。血瘀证“异病（冠心病、糖尿病）同证”的生物学基础可能与冠心病和糖尿病共同的病理机制密切相关。课题组前期运用核磁共振氢谱（1HNMR）等技术，获得冠心病血瘀证潜在的生物标记物，部分揭示血瘀证的生物学基础。本项目拟基于异病同证-共同土壤学说，以冠心病、糖尿病血瘀证为研究载体，运用代谢组学技术，阐明血瘀证“异病同证”的生物学基础，可为血瘀证的临床诊断提供新的思路和方法。研究：①运用系统生物学原理和方法，采用1HNMR等技术，寻找血瘀证患者“异病同证”的潜在的生物标记物，构建两者异常的整体代谢网络，阐明血瘀证的生物学基础。②通过分析血瘀证“异病同证”潜在的生物标记物、中医证候信息和生化指标的关联性，阐明血瘀证的证候本质。

慢性病已成为威胁我国居民健康的重要公共卫生问题，中医药防治慢性病具有独特优势。“异病同治”是中医学最重要的特色之一, “异病”能够“同治”的关键在于“病”虽异而“证”相同。临床上，慢性病具有共病性，可能存在共同的病理机制，即许多慢性病在病因病机上存在“共同的土壤”因此，“异病同治”的生物学基础可能与慢性病病因病机的“共同的土壤”密切相关。另一方面，在中医临床实践中，本项目基于“异病同治”中医经典理论，以冠心病、糖尿病的共同病理机制为切入点，运用非靶向代谢组学技术，揭示血瘀证“异病同治”生物学基础。本研究.1.纳入58例冠心病患者（27例冠心病血瘀证和31例冠心病痰浊证）。26例健康对照。通过比较冠心病两种中医证型以发现血瘀证潜在生物标记物。.2.纳入冠心病45例（其中冠心病血瘀证27例）、糖尿病45例（其中糖尿病血瘀证26例），正常对照组38例，通过比较异病（冠心病、糖尿病）同证（血瘀证）以发现血瘀证潜在生物标记物。.结果显示：1.胆碱、β-葡萄糖、α-葡萄糖、酪氨酸可能是冠心病血瘀证患者的潜在代谢物生物标志物。其中胆碱可以显著区分冠心病血瘀证和痰浊证。2. 谷氨酰胺，色氨酸，酪氨酸，柠檬酸，胆碱，α-葡萄糖，β-葡萄糖为冠心病与糖尿病共同的潜在生物标记物。涉及苯丙氨酸，酪氨酸和色氨酸的生物合成，丙氨酸，天冬氨酸和谷氨酸代谢，色氨酸及酪氨酸的代谢等，即两种疾病共同的土壤。通过分析冠心病血瘀证、糖尿病血瘀证潜在生物标记物，确定牛磺酸、α-葡萄糖、柠檬酸、琥珀酸、酪氨酸为血瘀证潜在生物标记物，即血瘀证异病同证生物学基础。.本研究初步建立了血瘀证患者代谢组学数据库，发现冠心病血瘀证、糖尿病血瘀证代谢组学特征，并明确冠心病、糖尿病病因病机的“共同的土壤”，揭示了血瘀证“异病（冠心病和糖尿病）同证”的生物学基础。