从冰片的一氧化氮生物活性探索其佐使作用内涵的实验研究

The Satsukai of Chinese medicine has been played a very important role in the prescription compatibility , It is a key part of developing new drugs and creating a new prescription. Borneol is the common Satsukai Chinese medicine for therapy Coronary Artery Disease(CHD).On the basis of Preliminary studies,Our team integrated the latest research results in nitric oxide (NO) research areas and the theory of Satsukai in TCM together, We proposed the hypothesis: "Borneol containing nitrite or nitrate reductase, it can double the overall efficacy of the prescription by Nitrate-Nitrate-Nitric oxide pathway, which result in a robust NO biological activity, Borneol bring the whole prescription to regulate the disease by the pathway, This may be the important mechanism for Satsukai role in TCM. In order to confirm this hypothesis ,Our team develop this study from whole body, organ, cell ,protein and molecular level by making use of molecular biology, herbs analysis and other means. We want to verify the hypothesis by exploration the NO biological activity of borneol before and after its compatibility, and exploration the borneol integrate prescription membership to regulate the disease by NO pathway as well as to confirm the borneol can reduce nitrite to rubost NO.By this way,We can reveal the nature of Satsukai role in TCM.This study will provide a theoretical and experimental basis for creating original new drug with TCM's characteristics and enhancing the efficacy of TCM prescription,Which will boost TCM saling to the international market, This research will also provide a new strategy and new ideal for the prevention and treatment of CHD as well as study it .

中药佐使在方剂配伍中具有十分重要的作用，是创制新方、开发新药的关键环节。冰片是治疗胸痹(冠心病)的常见佐使药，课题组在前期研究的基础上，将中医佐使理论与一氧化氮（NO）研究领域里的最新研究成果结合在一起，提出了："冰片具有独特的硝酸盐/亚硝酸盐还原性，它通过NO3ˉ-NO2ˉ-NO通道倍增整体方剂的疗效，产生强烈的NO生物活性，籍借传导途径引领诸药调节病所，这可能是冰片发挥佐使作用的一个重要机制"的假设。课题组利用分子生物学、药物分析等手段从分子、蛋白、细胞、组织及整体动物水平多层次递进式的展开研究。通过探索冰片配伍前后的NO生物活性、冰片配伍方药籍借NO传导通道靶向调控病所的作用机制、冰片的硝酸盐/亚硝酸还原性的确定从而验证假说，揭示冰片佐使作用的物质本质，为开发具有中医特色的原创新药、提升传统方剂疗效以及助推中药走向国际市场提供理论依据和实验基础，为冠心病的防治提供新的策略。

冰片是治疗胸痹(冠心病)的常见佐使药，课题组将中医佐使理论与一氧化氮（NO）研究领域里的最新研究成果结合在一起，提出了：“冰片具有独特的硝酸盐/亚硝酸盐还原性，它通过NO3ˉ—NO2ˉ—NO通道倍增整体方剂的疗效，产生强烈的NO生物活性，籍借传导途径引领诸药调节病所，这可能是冰片发挥佐使作用的一个重要机制”的假设。本研究采用冰片和治疗CHD常用中成药（复方丹参滴丸、通心络、速效救心丸、麝香保心丸以、冠心苏合胶囊）中的组成中药为研究药物，利用分子生物学、药物分析等手段从分子、蛋白、细胞、组织及整体动物水平多层次递进式的展开研究。药物分析结果表明，冰片含有少量硝酸盐，煮沸后检测到少量亚硝酸盐。蛋白层面结果证实，在无氧条件可阻断精氨酸经典通道，NO的产生主要通过补充通道。细胞层面结果显示，治疗冠心病的常见中药一旦与佐使药冰片配伍后，HCAEC细胞内的亚硝酸含量和NO活性显著提高，在无氧条件下效果更为显著。组织层面实验结果验证了不同中药组与冰片配伍后，其对血管的舒张程度明显增加，其中最高舒张比值达到100%。在心肌缺血的动物模型检测中发现，灌胃与冰片配伍的中药组，在保护心肌细胞凋亡上有明显作用。最终本研究验证了冰片作为佐使药，当机体出现缺氧状态时，其通过NO3ˉ—NO2ˉ—NO通道倍增了整体方剂的疗效的假说。同时揭示冰片佐使作用的物质本质，为开发具有中医特色的原创新药、提升传统方剂疗效以及助推中药走向国际市场提供理论依据和实验基础，为冠心病的防治提供新的策略。.

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