心理应激对大鼠实验性口腔溃疡愈合的影响及其干预的研究

Effect of psychological stress on the healing process of experimental oral mucositis in rats

目的探讨心理应激对大鼠实验性口腔溃疡模型黏膜组织愈合的影响及其干预的研究。方法雄性SD大鼠80只,正常对照组(Control)随机选取5只。其余75只随机分为口腔溃疡组(U)、口腔溃疡+心理应激组(U+S)、口腔溃疡+心理应激+药物组(U+S+M),每组各25只,每组再按照实验时间点分为0、24、48、72和120 h五个亚组。应激组以及药物组大鼠每日给予6 h束缚应激,连续应激1周。1周后,溃疡组、应激组以及药物组大鼠使用尖端直径为4 mm的单电电极灼烧大鼠舌体部建立实验性口腔溃疡模型,模型建立成功后按照时间点要求继续给予应激,同时药物组每日按1 mg/kg皮下注射地西泮。实验期间进行大鼠体质量测量、行为学检测、血清学检测,采用组织学和免疫组织化学方法分别观察口腔溃疡的组织病理学改变和热休克蛋白70(Hsp70)的表达情况。结果心理应激后大鼠表现出体质量增长减慢、行为异常、血清皮质酮及促肾上腺皮质激素浓度升高等一系列变化(P<0.05),心理应激影响下大鼠口腔溃疡的愈合进程减慢,炎细胞浸润高于对照组,血管及胶原再生均低于对照组以及Hsp70表达高于对照组、溃疡组(P<0.05)。结论心理应激能够延缓口腔溃疡黏膜组织的愈合进程,抗应激药物则可有效对抗心理应激在口腔溃疡愈合中的负性效应。

Objective To investigate the effect of psychological stress on the healing process of experimental oral mucositis in rats.Methods 80 male rats（ Sprague-Dawley） were randomly divided into four groups： 5 rats in control group（ Control）,75 rats in ulcer group（ U）,ulcer and stress group（ U ＋ S）,and ulcer and stress ＋ drug group（ U ＋ S ＋ M）,with 25 rats in each group. The rats with ulceration were euthanized at 0,24,48,72,and 120 h（ 5 rats per experimental period）. Psychological stress was induced by subjecting rats to restraint stress（ 6 h / d） for 7 consecutive days. Oral ulcer was induced by using a 4-mm tip monopolar electrode to cauterize in U,U ＋ S,U ＋ S ＋ M groups. Then,psychological stress was given to the rats in both U ＋ S and U ＋ S ＋ M groups at pointin-time continually. Also,diazepam was given to U ＋ S ＋ M group 1 mg / kg daily. The body weight gained,behavior tests and serum tests were used to testify stressed condition. Histological examinations were used to evaluate the changes of periodontal tissues and immunohistochemistry was used to evaluate the expression of HSP70. Results The stressed rats showed less body weight gained,abnormal behavioral changes and increased serum corticosterone（ CORT） and adrenocorticotropic hormone（ ACTH）（ P〈0. 05）. The surface of inflammatory infiltrate of the stress group was significantly higher than other groups and the expression of hsp70 in control and ulcer group was lower than in stress group（ P〈0. 05）. Conclusion Psychological stress can result in delayed healing process of the tissue in oral ulcer while diazepam might antagonize the stress and alleviate its negative effect.