蒙药小白蒿燥“希日乌苏”功效与抗炎作用机制的相关性研究

For a long time, the traditional medication experience and rich methods of treatment for "Xiriwusu" disease has been accumulated the traditional Mongolian medicine and pharmacy, which were clinical efficacy, and seldom poisonous effect, rich in resources. But now the challenging problem we have been facing is how to use the concept of modern medicine to explain the root cause of treating significantly the disease with Mongolian medicine possessing the drying "Xiriwusu" , namely the drug mechanism of action in vivo. Mongolian medicine used in this project is characteristic Mongolian medicine possessing the drying "Xiriwusu", Artemisia frigida, which was commonly used in history and folk. The cause of rheumatoid, rheumatism, head and limbs of chest trauma are caused by "Xiriwusu" and Artemisia frigida can be treatment of arthritis with conditioning blood and drying "Xiriwusu" in Sibuyidian. However, there is few reported scientific study to support these claimed therapeutic and medical effects, and not to mention the relationship between its drying "Xiriwusu" efficacy and anti-inflammatory effects. In this project, the anti-inflammatory and its molecular mechanism of total flavonoids from Artemisia frigida are studying in different ways and links of inflammation, and elucidate the correlation of drying "Xiriwusu" efficacy and anti-inflammatory effects for Artemisia frigida and determine the key site of drying "Xiriwusu" efficacy for Artemisia frigida, and provide a new idea for explaining the root cause of treating significantly the disease with Mongolian medicine possessing the drying "Xiriwusu" and a new method for the screening of anti-inflammatory Mongolian medicine

长期以来，在蒙医药学上"希日乌苏"病方面积累了丰富的治疗方法和传统用药经验，临床疗效显著，并毒副作用小、资源丰富。但目前面临着挑战性的问题就是如何利用现代医学理念来解释蒙医用燥"希日乌苏"蒙药治疗该病疗效显著的根本原因，即药物在体内的作用机制。本课题选择的蒙药是历代和民间常用的燥"希日乌苏" 特色蒙药小白蒿。四部医典中阐述了"类风湿、风湿、头四肢胸部外伤的病因都是沙日乌苏引起，小白篙能调理血液，兼燥"沙日乌苏"而治疗关节肿胀。然而，目前很少有科学研究来证实小白蒿这些治疗和药用功效，更谈不上其燥"希日乌苏"功效与抗炎作用的相关性。本项目从炎症的不同途径和环节对小白蒿总黄酮抗炎及其分子机制进行研究，阐明小白蒿澡"希日乌苏"功效与其抗炎作用的相关性，确定小白蒿燥"希日乌苏"功效的关键位点，为解释燥"希日乌苏"蒙药治疗"希日乌苏" 病疗效显著的根本原因提供一个新思路和为抗炎蒙药筛选提供一个新方法。

小白蒿是历代和民间常用的具澡“希日乌苏” 功效的特色蒙药。四部医典中阐述了“类风湿、风湿、头四肢胸部外伤的病因都是沙日乌苏引起，小白篙能调理血液，兼澡“沙日乌苏”而治疗关节肿胀。然而，目前很少有科学研究来证实小白蒿这些治疗和药用功效，更谈不上其澡“希日乌苏”功效与抗炎作用的相关性。本课题首先对小白蒿总黄酮的精制工艺及其化学成分进行了研究，通过单因素试验考查小白蒿总黄酮分离纯化主要影响因素，并采用正交试验确定了其最佳精制工艺。小白蒿总黄酮最佳精制工艺：样品浓度为2.72 mg/mL、上样量为40mL、洗脱流速为3mL/min和乙醇浓度为90%。为了摸清小白蒿总黄酮的主要化学成分，采用硅胶柱色谱法和半制备高效色相色谱法对小白蒿总黄酮进行分离，运用各种波谱法鉴定分离所得化合物的结构式。从其中鉴定了10个化合物：friginoside D、friginoside C、5-hydroxy-3′,4′,5′-trimethoxy-7-O-β-D-glucuronide、5-hydroxy-3′,4′-dimethoxy-7-O- β-D- glucuronide、槲皮素、木犀草素、5,7,3΄-三羟基-4΄-甲氧基黄酮、5,7,3΄-三羟基-6,4΄-二甲氧基黄酮、5, 3΄-二羟基-6, 7, 4΄-三甲氧基黄酮和5, 3΄-二羟基-3,6,7,4΄-四甲氧基黄酮，其中friginoside D和friginoside C为新化合物。在此工作基础之上，鸡蛋清致大鼠足肿胀、角叉菜胶诱发大鼠足跖肿胀、甲醛致大鼠足肿胀、棉球肉芽肿模型和免疫性炎症模型法检测小白蒿总黄酮对炎症发生抑制作用，确定了小白蒿总黄酮抗炎作用。在小白蒿总黄酮对炎症发生抑制的有效剂量下，小白蒿总黄酮对大鼠中性白细胞花生四烯酸代谢产物( Arachidonic acid metabolites) 的影响、对大鼠多形核白细胞（PMNL）细胞浆游离钙的影响和大鼠PMNL 内环一磷酸腺苷（cAMP） 水平的影响等抗炎的分子机制进行研究，确定了小白蒿澡“希日乌苏”功效的关键位点。本研究创建了一个澡“希日乌苏”蒙药抗炎作用筛选的新方法，为解释澡“希日乌苏”蒙药治疗“希日乌苏” 病疗效显著的根本原因提供了一个新思路。