调肝启枢化浊法防治糖尿病冠心病效应特点及机制研究

Diabetic coronary heart disease (DCHD), to which several risk factors including glucose and lipid metabolic disorders, obesity, hypertension and inflammatory factors contribute, is one of the diabetes macroangiopathies . Oxidative stress is a crucial part under the pathological condition..Intensive glucose lowering by single method can’t reduce macro-vascular events, while the treatment strategy in the existing guideline by multiple methods can’t reach satisfying efficacy. It’s of urgent need to explore a new therapeutic strategy and method..Chinese medicine has a natural advantage in these diseases, our previous studies confirmed that “Gan-depression and Pi-mis-transportation as fundamental, phlegm-damp-stasis stagnation as manifestation” is one of the basic pathogenesis of DCHD. We first proposed the method “TiaoGan QiShu HuaZhuo (Modulating Gan, to trigger Pi-hub with subsquent phlegm-damp-stasis clean)” as integrated control of glucose and lipid metabolism diseases and their vascular complications. Representative prescriptions of this method exert effects of multi-links and multi-targets on DCHD, by regulating lipid absorption, synthesization, transportation, transformation and excretion as well as regulating insulin signaling to ameliorate insulin resistance, anti-inflammation, anti-atherosclerosis, and so on. Relevant achievements have won the second prize of National Scientific and Technological Progress Award and National Outstanding Patent Award. .Base on the above, in this study, we intend to use molecular technology, glycomics and lipidomics etc., focusing on the key pathology of “glycolipid toxicity - oxidant stress”, to explore the effective profiles and mechanisms of the very “TiaoGan QiShu HuaZhuo” method on DCHD, using clinical trials, and in vivo/in vitro experiments. We expect to sum up some effective treatments with a series of prescriptions, meanwhile enriching TCM pathogenesis theory.

糖尿病冠心病（DCHD）是糖尿病大血管病变之一，与糖代谢紊乱、血脂紊乱、肥胖、高血压、炎症因子等多种危险因素关系密切，氧化应激贯穿其中。单因素强化降糖无法减少大血管事件，而现有指南中多危险因素控制治疗策略，亦尚未取得满意效果，探索新治则治法急迫而重要。中医药在此方面具有天然优势，项目组前期研究证实“肝郁脾枢失运为本，湿痰瘀浊内阻为标”是DCHD基本病机之一，首提“调肝启枢化浊”法综合防治糖脂代谢病及其血管并发症，代表方通过调节脂质吸收、合成、转运、转化、排泄和胰岛素信号通路、改善胰岛素抵抗、抗炎、抗动脉硬化等多环节、多靶点发挥作用，相关成果获国家科技进步二等奖和中国优秀专利奖。基于此，本项目拟运用分子生物学、脂、糖组学等方法，围绕“浊-氧化应激”核心病理，从临床、动物、细胞层次探讨调肝启枢化浊法防治DCHD效应特点和作用机制，以期提供一种切实有效的治则治法和相应方药，同时丰富中医病机学说。

针对糖脂代谢紊乱相关疾病的世界性难题，我们提出糖脂代谢病和“调肝启枢化浊”防治创新理论，得到同行广泛认可。本项目以“调肝启枢化浊”治疗糖尿病冠心病（DCHD）的效应特点及相关机制为主要目标，以人群研究结合动物模型，从“浊--氧化应激”角度开展系列研究，明确了DCHD“浊”的证候特点具体表现为“瘀浊、痰浊、湿浊、热浊”，证型以痰浊阻滞证、气阴两虚兼痰瘀证、心脉瘀阻证为主。基本阐明了调肝启枢化浊代表方FTZ调节糖、脂代谢，减轻冠脉狭窄，降低颈动脉内膜中层厚度、明显缓解胸闷、胸痛、气促等临床症状、抑制损伤部位的冠状动脉粥样硬化的发生发展，改善心脏器质和功能损伤，并能改善DCHD并发的肝、肾炎症和纤维化等综合效应特点；并揭示其通过抗炎、抗氧化应激治疗DCHD的分子机制。.本项目发表研究论文22篇，其中SCI6篇，主要代表作发表在糖脂代谢病和传统医学领域知名学术期刊如：Biomedicine & Pharmacotherapy、Chinese Journal of Integrative Medicine等；（2）申请发明专利3项，获得著作权3项；（3）人才培养成效显著：培养国家优秀青年基金获得者1人，珠江青年学者和珠江科技新星2人，晋升教授1人，副教授3人，培养博、硕士研究生14名；主办第三届世界中联代谢病专业委员会学术年会；并举办中医药防治代谢性疾病国际培训班；邀请英国利物浦大学糖生物学中心Jerry Turnbul教授讲学1次，项目组骨干成员参加国内外学术会议及交流10人次。.项目研究促进中医药防治DCHD研究，促进中医药防治DCHD诊疗水平的提高、为中医药防治糖脂代谢病提供了研究典范。