The Gender Dimorphism of Inflammatory Response Following Traumatic Hemorrhagic Shock: A study based on its functional genomics and validation of a novel therapeutic approach for post-traumatic multiple organ failure by hormonal modulation

• Main Authors: Yu-Ting Chung, 鍾侑庭
• Other Authors: 陳瑞杰
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/73350104375319432639

碩士 === 中國醫藥大學 === 醫學研究所碩士班 === 94 === Background：The majority of trauma patients in the acute and early categories died as a result of neurologic dysfunction, and hemorrhage. As all are known, the mortality rate of male following trauma is higher compared to that of females. A number of studies indicated that this sex difference was primarily the effect of sex hormones. The liver is a complex metabolically active organ, particularly susceptible to shock, and liver failure carries a high mortality rate. DNA microaray technology provide a pivotal tool in understanding the functional genomics of complex diseases. Purpose：Under the application of DNA microarray technology, we can have a global understanding of the pattern and difference of immune restoration and gene expression following traumatic hemorrhagic shock in the male and female rats. We also want to correlate these observed gene expressions with cellular change and clinical parameters such as hormone levels and serum cytokine concentrations. Methods：In our study, mature Sprague-Dawley rats with half for each sex, were divided into three groups, each group having 12 rats: group I: control group (sham operation); group II: hemorrhagic group; group III: resuscitative group . Hemorrhagic shock was induced by withdrawing blood via left femoral artery within 10 minutes and maintain MABP between 45-55 mmHg for one hour . The animals were sacrificed by euthanasia at 4 hrs after the finish of experiment to obtain the liver and whole blood. The liver samples were harvested for microarray analysis. The cytokines including TNF-α, IL-1β, IL-6, IL-10, as well as 17β-estradiol will be measured through the blood samples. Results: In shock group, the 4-hour mortality rate was 66.7% male subgroup and 50% in female subgroup. Amongthe mortality rats, male rats had shorter mean survival time than females did (81.3 min. vs. 123 min.). In regard to 17-β estradiol, plasma levels in females were significantly higher than those in males (p<0.001). Regardless of sexes, hemorrhagic group had the highest and control group had the lowest plasma levels of TNF-α, IL-1β, IL-6 and IL-10. In the microarray study, the GeneChip® revealed 4.1% (1283/31042) of assessed genes were altered. As compared with hemorrhagic group, the GeneChip® revealed 4.1% (1149/31042) of assessed genes were altered. Discussion: In shock group, the mortality rate was significant higher in male subgroup. Among the mortality rats, male rats had shorter mean survival time than females did. The current data of mortality and plasma levels of cytokines in shock group suggesting that females have more protective from traumatic hemorrhagic shock than males do. Except for the TNF-α, the gene expression in the liver were approximately in accordance with the corresponding cytokine levels in the blood. Most of the significant genes are energy producing and metabolically related genes, and some are signal transduction and matrix & structural proteins synthesis related. Conculsion: Female play an important role on modulation for systemic inflammatory response following traumatic hemorrhagic shock and resuscitation, therefore, reduce the early mortality of the injuried rats.