Effect Of Severe Burn Injury In The Glucocorticoid Receptor To Change Its Regulation Of The Molecular Mechanisms

The first response of body to severe trauma is stress, and the aim of it is to strengthen the resistance to the attack and resume the turbulence in the body. But the attack of severe trauma is so strong that the stress is usually in disorder. The disorder of stress could aggravate the crisis and lead to grave consequences. It was suggested that the disorder of stress play an important role in the ignition and development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). So it is necessary to explore and control the disorder of stress occurring in body following severe trauma. Glucocorticoid effect is one of the most important reactions of stress, and the executant of the effect is the receptor of glococorticoid. Olucocorticoid receptor (OR) expresses widely in the body and has the ability of restraining the release of chemical mediators and cytokines. So it plays an important role in controlling the inflammatory reactions in the body. Suffering strong attacks, the body would ignite inflammatory reactions to defend the attack. While, in order to avoid the inflammatory reactions being excessive and harmful, the body releases enormous eridogenous glucocorticoid to active OR to control the inflammatory reactions. Recently, it was reported that the expression of GR decreased after severe trauma. Down-regulation of OR would weaken its function of anti-inflammatory and impact the state of stress of whole body. So it is very valuable for us to deeply explore the mechanism of the change and regulation of GR to ameliorate the disorder of stress to prevent and cure ?11 ? systemic damage consequent upon severe trauma. In order to explain the characteristic and mechanism of change of GR duing the stress in body after severe trauma, and to find effective step to up- regulate the function of GR, in the present study, we used 3 5-40% TBSA- third- degree scalded rats as severe traumatic animal model. With methods of Western blot, immunohistochemistry, reverse transription polymerase chain reaction (RT-PCR), RIA, ELISA, and GRE-CAT transcription report system, we carried out the following experiments to do this study: ~ Analysis of characteristics of serumal corticosterone and inflammatory cytokines, and exploration of the change of GR during the stress after severe scalding; ? Investigation of mechanism of abnormal change of OR in rats suffering severe trauma; ?Exploration of the regulation of glucocorticoids on GR, and determination the best time and dose of glucocorticoids being used after severe trauma. Results and conclusions are sumarized as follows: 1. Corticosterone in serum significantly increased during the early stage after 3 5-40% TBSA-third-degree scalding, and reached the top at 2-4h after scalding. TNF- a, IL-i P and IL-6 also increased, and there was a secreation peak of TNF- a and IL-i P at 1 5mm and a peak of IL-6 at 3 0mm after scalding. While the expression of OR in the liver, lungs and hippocampus was markedly decreased after severe scalding. These results suggest that the body is in a state of stress with high glucocorticoids, high inflammatory cytokines and low OR, and this state is harmful to the body for it tends to induce systemic damage. 2. The expression of OR in liver obviously decreased at 30mm after 35- 40% TBSA-third-degree scalding, and reached the nadir at 4h, and until 96h...