肠源气道平滑肌解痉物质

我国哮喘和COPD患者共计约1.457亿，全世界5.327亿，而且两病发病率均呈上升趋势，因此，气管扩张剂需量极大，但目前的具有从无效到诱发死亡等严重副作用，所以，亟需更好的气管扩张剂。我们发大鼠和小鼠肠道粗提物可完全解除小鼠气道平滑肌最大痉挛性收缩，解痉能力远超常用的长、短效气管扩张剂福莫特罗和沙丁胺醇，此外，它存于体内，副作用可能较小。因此，我们提出肠道中具有更好气管扩张剂的假说。为求证，我们利用掌握的各种技术，首先从小鼠（以及猪、牛和人）的肠道分离纯化鉴定出这种物质并解析其分子，之后利用哮喘小鼠模型和人的气道平滑肌评估是否是更好的气管扩张剂，最后在小鼠气道平滑肌阐明解痉机理。预期结果及意义：发现肠道有更好的气管扩张剂这一新现象；为未来制药发现供源，也为将来合成或寻找天然来源提供分子指纹；开创从肠道角度研究哮喘和COPD气道平滑肌异常收缩的形成机制及防治的新领域。

There are 145.7 million asthma and COPD patients in China, and 532.7 million in the world, moreover, the morbidity of two diseases is increasing gradually. Therefore, there is a great demand for bronchodilators. However, the currently used bronchodilators have serious side effects from no efficacy to induce death. Thus, it urgently needs for better bronchodilators. We have found that the crude extract of the intestines of rats and mice completely relieved the maximal spasmodic contraction of airway smooth muscle of mice, such capability of relieving spasm was far more beyond that of the commonly used long- and short-acting bronchodilators formoterol and salbutamol. In addition, intestinal substances of relieving spasm exist in the body, thus, which should have less side effects. Therefore, we propose the hypothesis that there are better bronchodilators in the guts. To prove it, we will use all kinds of techniques we are familiar with, firstly to separate and purify the substances from the intestines of mouse (and swine、cattle and human) and then identify their molecules; then to evaluate whether they are better bronchodilators in a mouse model of asthma and human airway smooth muscle; finally to determine the mechanism of relieving spasm in mouse airway smooth muscle. Expected results and significance: a new phenomenon that there are better bronchodilators in the guts will be discovered; sources used for making drugs will be defined, and molecular fingerprints for the future synthesis or search for natural sources will be provided; a new field to study the mechanism and prevention of abnormal airway contraction occurring in asthma and COPD from the intestines will be opened.