【作者】 韩荣；

【导师】 周铭心；

【作者基本信息】 新疆医科大学 ， 药理学， 2011， 博士

【摘要】 目的：宗转化医学理念,本“涤其体而达其用”的思想,在“血脉微型癥瘕”概念提出的基础上立软坚散结,消积去腐法拟以新疆地产药物阿魏为君药的中药处方,并基于现代理论技术,通过拟临床及临床研究评价中医药治疗高脂血症的有效性及安全性,以此证明：1)理论创新是提升中医临床疗效的关键所在；2)转化医学模式对中医学的发展具有积极的指导意义。方法：1)在对中医古今文献中高脂血症的病因病机辨证分型以及临床试验进行系统评价。2)通过建立动物病证模型进行拟临床研究。3)通过多中心、随机、双盲、安慰剂平行对照设计的临床研究,确定软坚散结消积去腐法治疗高脂血症的有效性和安全性。结果：1)6054例高脂血症病例调研结果显示：痰瘀互结、痰湿(浊)内阻、脾虚湿盛为主要证型,占57.46%。RCT临床研究显示：中药治疗高脂血症血脂疗效平均有效率为76.86%。TG平均降低0.83±0.49mmol/L。未见中药治疗导致肝肾功能异常的病例报道。2)建立了阿魏胶囊的指纹图谱；阿魏胶囊降低正常和高脂血症动物TC、TG、LDLC,升高HDLC(P<0.05或P<0.01),并能预防高脂饮食动物血脂异常。连续给药6月,高剂量组脾功能亢进,RBC、HGB、HCT下降,停药1月后恢复。体外细胞毒试验结果显示：药物作用后,细胞增殖。3)临床研究结果显示,血脂疗效平均有效率为74.50%,中医证侯疗效有效率为79.19%。中药组服药前后TC、TG、HDL-C、LDL-C差异均有统计学意义(P<0.05或P<0.01),TG下降0.8503±1.803mmol/L。结论：1)从“涤其体而达其用”的思想出发提出“血脉微型癥瘕”学说立软坚散结、消积祛腐法在高脂血症的治疗中独辟蹊径,并在此基础上研制的阿魏胶囊治疗高脂血症安全有效,且质量可控。说明理论创新是促进中医药发展的核心。2)拟临床及临床研究结果均显示阿魏胶囊具有调节血脂作用,其中降低TG作用尤为明显。3)基于中医理论创新及创新理论指导下的理法方药,借助现代技术和方法进行研究和评价,得出末端指标明确,安全、有效、质量可控的现代复方中药制剂。以此证明,转化医学模式对中医临床水平的提升具有积极的指导意义。更多还原

【Abstract】 Aim:Apply the translational medicine principles and methods, based on "ignore the nature of a drug and to emphasize on drug usage" thought, accordance to "Blood vessel midget mass" conception propose softening hardness and dissipating mass, esolving accumulation and eliminating pus and necrotic tissues, cooling blood to remove apthogenic heat method and use Chinese medicine prescription contain Ferula asafoetida L as a principal drug for treatment hyperlipoidemia, also applied clinical-mimetic research and clinical research to evaluation the Chinese medicine efficacy and safety on treating on hyperlipoidemia. 1)Theory innovation is is crucial to promote the Chinese medicine curative effect.2) Prove translational medicine model has prevalent meaning of guidance to Chinese medicine development. Method:1) The pathogeny, pathogenesis and differentiation of symptoms and signs for classification of syndrome on hyperlipoidemia of the traditional Chinese medicine dynasties literature were systematically evaluated.2) Establish diseases animal model conduct the clinical-mimetic research.3) A Multi-center, Randomized, Double-blind, Placebo-controlled, Clinical Trial was adopted to evaluation the efficacy and safety of Ruanjiansanjie (softening hardness and dissipating mass) therapy method treating for hyperlipoidemia. Results:1) 6054 cases of hyperlipoidemia were selected for this study, the results showed that: Intermingled Phlegm and Blood Stasis, Resistance within the sputum wet muddy, Spleen Dysfunction due to Dampness is main syndrome, account for 57.46%. the clinical trial results showed that the total efficacy of Chinese medicine treatment for hyperlipoi-demia was 76.86%Decrease the TG average 0.83±0.49mmol/L。did not found adverse effect to main organ such as liver and kidney.2) a fingerprinting map of Ferula asafoetida L was also made, Ferula asafoetida L can decrease the normal rat and hyperlipoidemia animal model TC TG、LDLC, increase HDLC (P<0.05), and prevent high fat diet cause abnormity of plasma lipid. Administrate for six month period the high dosage group has hypersplenia, RBC、HGB、HCTdecresing, but recover after discontinuation of medicine。cytotoxicity test results showed that the medicice induce cell proliferation.3) clinical trial results showed that the average efficacy was 74.50%, the Chinese syndrome effecay was 79.19%O there was significantly different between those in the pre-and post-treatment TC、TG、HDL-C、LDL-C (P<0.05 or P<0.01) in chinese medicine treatment group, TG was decreased at 0.8503±1.803mmol/L. Conclusion:1) Based on "ignore the nature of a drug and to emphasize on drug usage" thought, "Blood vessel midget mass" theory san support the softening hardness and dissipating mass, esolving accumulation and eliminating pus and necrotic tissues, cooling blood to remove apthogenic heat method for hyperlipoidemia and open a new road for Chinese treatment for hyperlipoidemia. Additionally the new Chinese medicine "Awei capsule " was developed according the theory for treatment hyperlipoidemia, the medicine has safety, effecay, quality controllable. This results can explain theory innovation is core of Chinese medicine development.2) clinical-mimetic research and clinical research results showed that "Awei capsule" has lipid regulation effection, among them remarkedly decerease TG.3) based on Chinese medicine theory innovation and innovation theory guide to Chinese prescription, also apply modern techniques and method to research and evaluate Chinese prescription, can develop safety, effective, quality controllable modern Chinese medicine. The study is not only of important theory value, but also translational medicine positive reality meaning to improve the Chinese medicine,更多还原