The Role of Psychologic Stress‐Induced Hypoxia‐Inducible Factor‐1α in Rat Experimental Periodontitis

Background: Studies have shown that psychologic stress plays a significant role in the outcome of many diseases. The present study is designed to investigate the effect of stress on experimental ligature‐induced periodontal disease in rats by means of a variable moderate chronic stress model. Methods: Sixty‐six age‐matched male Wistar rats of specific pathogen‐free grade were randomly divided into four groups: 1) normal control group, naive rats; 2) experimental periodontitis group, received only silk ligatures at the gingival margins of the second maxillary molar; 3) stress‐stimulation group, treated only with experimental stress conditions; and 4) experimental periodontitis plus stress‐stimulation group (e.g., experimental groups also exposed to stress). Stress was imposed by means of restraint stress, cold‐water immersion stress, and cat shock stress, which were all applied randomly. The rats were sacrificed at weeks 1, 4, 6, and 8 of the experiment. Attachment losses (AL) were measured by a specially made periodontal probe. The histopathologic changes of periodontia stained with hematoxylin and eosin were observed under a microscope. The expression of hypoxia‐inducible factor‐1α used to evaluate tissue hypoxic degree in periodontal tissues was tested by immunohistochemistry. Results: Our results show that there was no significant difference of AL among the normal control and the stress‐stimulation groups ( P >0.05); AL of the periodontitis plus stress‐stimulation group was significantly higher than that of the experimental periodontitis group at weeks 4, 6, and 8 ( P <0.01), and the hypoxia‐inducible factor‐1α expression scores of the periodontitis plus stress‐stimulation group were significantly higher than those of the experimental periodontitis group at weeks 4, 6, and 8 ( P = 0.0477). Conclusions: Stress‐stimulation may aggravate periodontitis by decreased tissue oxygenation in rats. We conclude that there is a correlation of periodontitis severity with psychologic stress and periodontal tissue hypoxia.