HIF-1α-ROS-NF-κB信号通路介导心理应激加重牙周炎病变的作用机制研究

牙周炎是导致成年人牙齿丧失的首要原因。近年，其病因学中的心理因素逐渐受到人们关注。我们前期研究发现心理应激可以加重牙周炎组织病变，但调控机制尚不清楚。缺氧诱导因子-lα(HIF-1α)是缺氧应答关键因子，能够影响活性氧(ROS)代谢水平，而参与炎性反应的核转录因子-κB(NF-κB)对氧化还原失稳态敏感。我们早期针对口颌肌实验曾证实组织缺氧和氧化还原反应异常可由心理应激诱导发生。牙周炎过程中也常伴有局部氧化损伤，因此，HIF-1α-ROS-NF-κB信号通路很可能在心理应激加重牙周炎病变中扮演重要角色。本项目拟建立动物心理应激模型和牙周炎模型，观察并明确心理应激时牙周炎组织的氧代谢和氧化还原状态以及炎性反应程度，并通过体内、体外实验探讨HIF-1α-ROS-NF-κB信号通路在心理应激加重牙周炎局部病变过程中的可能作用机制，为研究牙周炎的心理病因学发病机制及有效防治提供新的实验依据和策略。

Periodontitis is the leading cause resulting into tooth loss in adult. In recent years, the influence of psychological factor on periodontitis is catching more and more attentions. We have confirmed that psychological stress could aggravate the periodontitis via further deteriorating the physical structure of periodontal tissue and delaying the elimination of local inflammation. However, the underling mechanism is still unclear. Hypoxia-inducible factor -1α (HIF-1α) which could affect the metabolism of active oxygen species (ROS) is considered to be the key factor response to hypoxia, while nuclear transcription factor-κB (NF-κB) is redox-sensitive and active in the inflammatory process. The hypoxia and oxidative damage in masticatory muscle in rats after psychological stress have been reported in our precious studies. With the fact that periodontitis is also often accompanied by local oxidative damage, we speculate that local HIF-1α-ROS-NF-κB signaling pathway is likely to play an important role in the aggravating process of periodontitis induced by psychological stress. For verifying the hypothesis, we will establish the rodent psychological stress model and experimental periodontitis model. Based on the systematic observation of the adverse influences of psychological stress on the periodontal tissue during periodontitis process, the local oxygen metabolism, redox state and inflammation of periodontal tissue will be clarified with the methods of tissue morphology and molecular biology. Additionally, the potential regulatory mechanism of HIF-1α-ROS-NF-κB signaling pathway during the aggravating process of periodontitis induced by psychological stress will be investigated in vivo and in vitro. The whole project is expected to provide new experimental basis for understanding the role of psychology in the etiology of periodontitis as well as related preventive measures in the future.