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-1 alpha 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-1 alpha 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. J Periodontol 2011;82:934-941.