Application of Gene Expression Analysis with Microarrays and Proteomics to the Problem of Hemorrhagic Shock and Resuscitation

摘要

Hemorrhage is the principal cause of death of soldiers on the battlefield. With dispersed troops and future combat operations expecting longer evacuation times and limited availability of medical supplies far- forward, significant improvements in fluid resuscitation will be required if casualties are to be saved. While it is known that a drop in blood pressure below 40 mm Hg or loss of more than 50% of the blood volume is fatal, most cells in the body, with the exception of brain cells, can survive for several hours with minimal oxygen or nutrients. Hence, morbidity from blood loss involves factors beside lack of oxygen and nutrients. Little more is known, however, about how the body responds to loss of blood or which organs are most affected. An understanding of the temporal responses of tissues to hemorrhage will lead to improved strategies of intervention before irreversible deterioration occurs. We are using gene expression analysis with microarrays to assess the responses of various organs to severe hemorrhage in rodents to uncover the prominent metabolic pathways involved. Until recently, traditional molecular techniques allowed analysis of only one gene at a time. Throughput was very limited and an accurate picture of the molecules that orchestrate the regulation of health and the dysfunction that occurs during disease or injury has not been possible. The microarray, which allows analysis of changes in expression of thousands of genes, promises to help clarify the molecular and genetic basis of health and disease and speed drug discovery. This information will guide the rational development of new resuscitation fluids with appropriate drug additives.