The Effects Of Chronic Restraint Stress On Acute Gastric Mucosa Injury Induced By WIRS And Its Healing

BackgroundStress ulcer (acute gastric mucosal injury) are common in critically patients in clinical complication occurs especially in severe burn trauma, major surgery, severe brain injury, serious infections and other acute and severe groups.After long time research scholars pointed out that acute gastric mucosal injury primarily associated with the following aspects:neuroendocrine disorders, gastric acid secretion, reduced PG and NO other protective factors, increased production of reactive oxygen species, gastric mucosal cell proliferation/apoptosis imbalance and so on. Our group long-term commitment to research and acute gastric mucosal injury and healing, pre-prepared by immersion restraint stress model (WIRS) occurs, the impact of simulated stress injury in rats with gastric ulcer development and discuss its possible mechanism and the level of control from the stress, find some common pretreatment anesthetic, sedative drugs, such as sufentanil, ketamine, dextromethorphan care pyrimidine can be effectively protected AGML, So there are some non-invasive stress in surgery and anesthesia, such as stress, anxiety, fear and a series of psychological stress, these will not affect the acute gastric mucosal injury? Its mechanism of stress and how? Psychological stress (psychological stress) is cognitive, a physical and mental evaluation capacity at individual stressors perceived threat caused by tension, tension continued this body cardiovascular and cerebrovascular disease, neuroendocrine disorders, immune system disorders play an important role. The models of Psychological stress include flooding, Restraint, noise, electric shock, but some of the physical stress components exist, and restraint stress as a non-invasive stimulation, can simulate the human life "can not control "crowded, frustration and other living conditions, therefore, restraint stress is a good psychological stress model. The main topic to prepare psychological stress model of acute gastric mucosal injury was observed and the more and the possible mechanism by restraint stress, psychological stress to determine cause gastric mucosal injury provide a reliable basis, which leads to gastric mucosa from the restraint stress possible causes damage, discusses the appropriate intervention and treatment; Not only Provide new signaling pathways and academic point of view, but also offer new therapeutic targets and strategies on preventing the occurrence and development of AGML.ObjectiveThrough for coping chronic restraint stress and water immersion restraint stress model on rats, and analyzing the possible cause of the gastric mucosa damage, such as oxygen free radical damage、cell proliferation and apoptosis imbalance. Preliminary exploration:1. The effects and possible causes on normal gastric mucosa of rats for different time of chronic restraint stress; 2. The effects and possible causes on AGML of chronic restraint stress; 3.The effects and possible causes on the healing of AGML for chronic restraint stress.Methods(1) 32 adult male SPF Wistar rats, and randomly divided into 4 groups, namely: normal group (NC group),3 d stress group (RS3) and 5 d group (group RS5) bondage stress and bondage stress 7 d group (group RS7). Excepting the NC group, preparation of restraint stress model, recording weights every day. The details were as followed.:1 After anesthesia, Collecting gastric juice and counting the ulcer index; 2.Observe the gastric tissue morphology; 3 Using real-time quantitative PCR method to detect the expression of PCNA mRNA and Caspase-3 mRNA.4 Collect the abdominal aortic blood in order to measure SOD and MDA levels.(2) 32 adult male SPF Wistar rats, and randomly divided into 4 groups, respectively:normal group (NC group), flooding bondage stress group (group WIRS), chronic bondage stress group (RS) and chronic bondage stress after immersion bondage stress group (RS+WIRS group), two groups are preparing to bondage stress model,7 days WIRS and RS+WIRS group are preparation of flooding bondage stress model. Experiment with the first part.(3) 64 adult male SPF Wistar rats, and randomly divided into 8 groups, respectively is:the normal group (NC group), flooding bondage stress group (group WIRS), flooding bondage stress after 3 d (WIRS3 group) and 5 d group (WIRS5),7 d group (group WIRS7), flooding bondage stress after chronic bondage stress group (WIRS+RS3)3 d,5 d group (WIRS+RS5),7 d group (WIRS+RS7 group), in addition to the NC group, preparation of flooding bondage stress model, the RS group are preparing to bondage stress model. Experiment with the first part.Results(1) Compared with group NC,gastric mucosal in Group RS was injured more seriously, the UI and water content and the restranit time had aproportional relation; Compared with group NC,groups RS rat serum and SOD were increased, and with prolonged restraint, SOD decreased, but the serum and mucosal MDA were increased (P<0.01); The expression of PCNA were decreased in group RS, but the Caspase-3 were increased.(2) Compared with group NC, varying degrees injured were appeared in other three groups, especially in group RS+WIRS; Compared with group WIRS, the serum SOD/MDA and the PH and the expression of PCNA were no statistically significant difference in group RS+WIRS; but the expression of Caspase-3 were increased significantly.(3) Compared with group NC,gastric mucosal in Group WIRS was injured most seriously,and there were 7days for repair; group S3 were healing better than group F3, but group S7 were healing worse than group F7;Compared with group WIRS, the MDA and SOD were lowed with the time,and the PH were increased; Compared with group F3, the SOD/MDA and expression of Caspase-3 were have no statistically significant difference in group S3, and the expression of PCNA were increased significantly;Compared with group F7, the SOD/MDA and expression of PCNA were decreased significantly in group S7, while increased in expression of Caspase-3; And the PH were increased in group S, when compared with group F.Conclusion:(1) Chronic stress can cause gastric mucosa structure damage, and damage degree and the time is, it is not only related to cut SOD/MDA value of gastric mucosa, and chronic bondage stress also cause gastric mucosa apoptosis significantly increased, decreased proliferation is related to the imbalance between them are the important reasons for ulcer;(2) Chronic bondage stress pretreatment can aggravate the acute gastric mucosa injury induced by WIRS, this mainly with chronic bondage stress may cause the gastric mucosa epithelial cells apoptosis.(3) Rats after immersion bondage stress induced gastric mucosal injury by about 7 days can achieve basic returned to normal, the function of gastric mucosa recovery still need to extend the time; Early chronic bondage stress can accelerate the healing of gastric mucosa injury, but with the prolonged will delay the healing of injury, this may be related to stress early can promote gastric mucosa epithelial cell proliferation, and with the increase of stress intensity, gastric mucosa epithelial cell apoptosis more, cause delayed healing.