肥大细胞调控哮喘小鼠深静脉血栓形成的作用及关键机制研究

Recent studies suggest that the incidence of deep venous thrombosis (DVT) in asthmatic patients is higher than those without asthma, however, there is no empirical evidence to support the precise relationship between them and the related mechanisms. In the condition of asthma, mast cells (MCs) are activated to release sensitized and inflammatory factors, leading to endothelial dysfunction, which plays an important role in triggering DVT. Based on the mice asthma model and mice DVT model, we found that wild-type asthmatic mice formed obvious DVT compared with the normal wild-type mice, and mast cells depleted asthmatic mice did not form obvious DVT. Therefore, we raise up the hypothesis: mast cells may play an important role in the formation of DVT in asthmatic mice. This study intends to further clarify the role of MCs in the formation of DVT in asthmatic mice, and verify the key signaling pathways in the formation of DVT in asthmatic mice. These findings may provide theoretical gist into the prevention and treatment of DVT for asthmatic patients.

近期研究提示哮喘患者深静脉血栓（DVT）发生率升高，然而目前缺乏针对此类血栓形成及其机制的研究。哮喘状态下肥大细胞（MCs）活化释放致敏及致炎因子，与血管内皮功能紊乱密切相关，后者为促发DVT形成的始动因素。我们课题组前期构建小鼠哮喘模型和小鼠深静脉血栓模型，发现野生型哮喘小鼠相比野生型对照小鼠，DVT形成更明显，而肥大细胞消耗的哮喘小鼠总体未形成明显血栓。据此我们提出设想：MCs在哮喘小鼠DVT形成过程中扮演重要角色。本项目拟进一步明确MCs在哮喘小鼠DVT形成过程中的作用，并通过动物和细胞实验进一步验证关键信号通路在哮喘DVT形成过程中的作用。本项目的研究发现可能为哮喘人群DVT的防治提供理论依据。

研究发现哮喘患者深静脉血栓（DVT）发生率升高，然而目前缺乏针对此类血栓形成及其机制的研究。本课题我们基于稳定构建的小鼠哮喘模型和下腔静脉DVT模型，卵白蛋白（OVA）诱导的野生型哮喘小鼠相比对照野生型小鼠，DVT明显加重，说明哮喘可能会导致DVT发生发展。而OVA诱导的肥大细胞（MCs）缺陷小鼠血栓明显减轻，表明MCs与哮喘小鼠DVT形成密切相关。抑制野生型哮喘小鼠MCs脱颗粒后，血浆组胺水平明显下降，DVT形成明显减轻，而输注野生型小鼠来源的MCs后，血浆组胺和DVT变化趋势逆转，表明哮喘小鼠DVT发生和MCs脱颗粒有关。哮喘状态下MCs活化释放致敏及致炎因子，与血管内皮功能紊乱密切相关，后者为促发DVT形成的始动因素。本研究可观察到哮喘小鼠相关血浆炎性因子水平升高，与MCs脱颗粒有关，表明全身炎症反应可能也是MCs参与哮喘DVT发生发展的重要机制。本项目的研究发现可能为哮喘人群DVT的防治提供理论依据。