| Gradually stinging competition of society, fast pace of life and the poor state of their own become the source of all kinds of physiological and psychological stress of the modern people. Long-term or excessive psychological stress is harmful to the body, even lead to a series of disease. Numerous studies have confirmed that psychological stress and excessive mental pressure are risk factors or influence elements of systemic disease. Long-term psychological stress can lead to the low immunity of the body, causing the body's immune response. Studies have confirmed that the psychological stress as a kind of bad stimulation factors, when under stress, the sympathetic nervous excited, HPA axis activation, inhibition of cellular immunity and enhance the humoral immune, having an effect on the body's immune system and leukocyte activation, meanwhile changing the levels of inflammatory cytokine release, delaying fibroblast differentiation, extending the healing process of skin and mucosa. The morbidity of oral mucositis is the top among the oral mucosa disease, which influence the patient's quality of life seriously. However, etiology and pathogenic are still unknown. The results of personality questionnaire have showed that the most recurrent patients with ulcer disease have obviously important life events within a year, so oral mucositis is closely related to psychological reaction. As a kind of bad factors, causing abnormal immune response, stress plays a significant role in the development of oral mucositis. So what's the role of psychological stress played in the healing process of oral mucositis and its mechanisms, still remain unknown. There are three parts of experimental in the present study:Part 1. The establishment and evaluation of the psychological stress animal models and experimental oral mucositis models in rats.Eighty male rats(Sprague-Dawley) were randomly separated into four groups, as follows: control group; ulcer group; ulcer and stress group; ulcer and stress+drug group. The rats with ulceration were euthanized at zero point and 24, 48, 72, and 120 h(5 animals per experimental period). Psychological stress was induced by subjecting rats to restraint stress(6h/d) for 7 consecutive days. We induced oral ulcer by using a 4-mm tip monopolar electrode to cauterization in ulcer group, stress group and drug group. Then, Psychological stress was given to the rats in stress group and drug group at point-in-time continually. Also, Diazepam was given to drug group 1mg/Kg daily. We used the body weight gained, behavior tests and serum tests to testify stressed condition. The results showed that less body weight gained in the stress group than that in the control group; the restraint stress induced an obvious behavioral changes and increased serum corticosterone(CORT)and adrenocorticotropic hormone(ACTH).The result indicated that chronic restrain stress could result in stressed condition of rats and ensured the progress of the following experiments. After cauterization, ulceration organization was in the tongue body, overlying yellow pseudomembrane, surrounded with hyperemia flushed zone and the central depression, that conformed to the clinical characteristics of oral ulcer. Histological results showed a large number of inflammatory infiltrate, collagen fibers edema and collagen deposition. The result indicated that this method was effectively.In present study,by establishing the animal modle of restraint stress in rats, using the behavioral tests, Elisa tests, histopathology and immunohistochemical, we explored the effects of psychological stress on the development, healing and the expression of influence healing effect factors of oral ulcer, using anti-stress drug to antagonize the adverse effects of psychological stress.Part 2. The influence of psychological stress on the healing process of experimental oral mucositis in ratsIn this part of the experiment, we observed tongue mucosa by general observation and histopathology. At 0h there were no significant differences between the groups. The tongue mucosa showed an ulcerated epithelium covered by necrotic tissue with intense inflammatory exudate composed mainly of neutrophils. Moderate to intense hyperemia and edema were observed in the lamina propria. Discrete to moderate angiogenesis was noted mainly in the ulcer basis. At 48 h granulation tissue, angiogenesis and collagen deposition in ulcer group were significantly more intense than in ulcer+stress group. At 72 h in ulcer group, the edema of epithelial disappeared. Inflammatory infiltrate reduced composed mainly of neutrophils with mild epithelization. Amount of new collagen were in the lamina propria with granulation tissue and intense angiogenesis. Compared with ulcer group, the repair process was bad in stress group. Inflammatory infiltrate was obvious, the arrangement of collagen fibers was disordered in the lamina propria. Compared with ulcer+stress group, obviously inflammatory infiltrate induced, intense collagen deposition and angiogenesis can be observed in the lamina propria in drug group. The result indicated that psychological stress have negative effect on healing process of oral ulcer, while anti-stress drug have an positive effect on antagonizing of psychological stress on healing process.Part 3. The molecular mechamisms of the influence of psychological stress on experimental oral mucositis in ratsIn this part of the experiment, immunohistochemical staining was used to detect the expression of HSP70 and EGF in the ulcer tissues. The results of HSP70 showed that there was a mild number of HSP70-immunoreactive cells at each time point in normal control group. While, the number of HSP70-immunoreactive cells in ulcer group was moderate. At 72 h, the expression of HSP70 reached at high spot in ulcer+stress group. The number ofHSP70-immunoreactive cells in drug group were more than stress group.Meanwhile,the results of EGF showed that there was a moderate number of EGF-immunoreactive cells at each time point in normal control group. After cauterization, EGF-immunoreactive cells increased in other groups. There was a significantly rebound in ulcer group and slowing of recovery in stress group of the number and staining intensity of EGF-immunoreactive cells. At the same time, the expression of EGF in the drug group was stronger than that in stress group.Conclusions:1. Psychologically stressed condition and a series of biological changes are all caused by chronic restraint stress in rats. Experimental oral mucositis model is established in rats by cauterization.2. Psychological stress have an effect on the healing process of ulcer tissue by slowing down the elimination of the inflammation, collagen deposition and angiogenesis, influencing oral mucous tissue repair.3. In oral healing process, the expression of HSP70 of mucous tissue increases because of psychological stress, suggesting that HSP70 have an effect on oral mucous tissue repair.4. Psychological stress can induce the expression of EGF of mucous tissue in oral healing process, suggesting that this may be one of the mechanisms that psychological stress can delay oral ulcer healing.5. The adverse effects of psychological stress are antagonized by anti-stress drug diazepam effectively. |
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