Evaluation Of Polymorphism In Hsp90 Functional Region And Its Effect On The Stress Competence Of Mice

Stress, a comprehensive adaptable response of the organism to harmful stimuli, is well understood as the adaptable changes of the multiple internal environmental homeostatic axes of the organisms including hypothalamus-pituitary-adrenal (HPA) axis for the purpose of increasing -stress resistance. It is well-known that different individuals and germ lines may have different stress competence to the same stimulus, and hence stress competence and secondary injuries to the organisms suffering from trauma stress may be significant different because of different genetic backgrounds. The studies of the intervention, controlling methods of the stress difference have been a hot topic for researchers. When stress of the organism occurs, remarkable changes of the Gc-GR effect are caused, which is closely related with stimulating levels and the Gc-GR effect is also related with the reaction levels. Chaperone protein heat shock protein 90s(Hsp90s), an indispensable protein in the pathway of Gc-GR effect, plays an important modulating role in the processes such as maturing of GR protein, maintenance of conformation, GR ligand conjugation, nucleic translocation of Gc-GR compound and intranuclear circulation.It has been reported that two strains of C57BL/6 and BALB/c mice with identical genetic background possess not only the differences of early post-trauma reactive heterogeneity, post-trauma inflammatory reaction and wound healing but also different immunologic reactions to the same ectogenic immunogen, which closely related with Gc-GR effect is confirmed. The main purpose of this study was to explore the etiopathology of the difference of Gc-GR effect, the specific affecting factors and its effect on the post-traumastress difference between the two strains of C57BL/6 and BALB/c mice.The systemic blast injury (SBI), was used to esplore alterations of Gc-GR signal pathway of BALB/c and C57BL/6 mice in the three main aspects: Gc level, GR level and nucleic/cytosol distribution and chaperone Hsp90 pre- and post-stress as well as the effect of constructional difference of isomer HSP90 in Hsp90s on post-trauma stress difference. The conclusions of the study are as below:1. SBI trauma model, applied in our study, is an ideal model for the study of post-trauma stress with advantages such as identical causative factors of injury shock wave in same environment, no need of anesthesia, easy repeated manipulation and large number of animals injured simultaneously.2. By observation of the death rate phenotype of C57BL/6 and BALB/c mice after SBI trauma stress, The stronger adaptability to stress in C57BL/6 mice than BALB/c were confirmed and the difference mainly presented within 6 h post-trauma stress.3. Analysis of Western blot demonstrated that the relative ratio of cell nucleus to cytoplasm of GR protein in the brain tissue of C57BL/6 mice within 6 h after SBI was significantly higher than that of BALB/c mice but no difference at 24 h after SBI, suggesting that efficiency of GR nucleic translocation in the brain tissue of C57BL/6 at early stress stage was higher than that of BALB/c mice. Besides, the GRE conjugating activity of cell nucleus extract from the brain tissue of C57BL/6 after SBI was higher than that of BALB/c mice was found with EMS A. The above indicated that there was significant difference of Gc-GR effect in GR nucleic translocation and GRE conjugating activity between the two strains of mice, which might result from the stress difference of the two strains of mice.4. After SBI stress, the concentration of cortisol in murine blood serum rapidly increased at 0.5 h and gradually fell and reached the pre-SBI stresslevel before 72 h. The post-SBI content of Hsp84 in cytoplasm in the brain tissue of the two strains of mice was remarkably higher than that before SB1, but no significant difference was found before and after SBI in cytoplasm in the brain tissue. There was no significant difference of the above parameters between the two strains of mice, suggesting that Gc contents in...