الفهرس | Only 14 pages are availabe for public view |
Abstract Trauma is the principal cause of death for people under 35 years of age, with more than 5 million injury-related deaths every year in the world. Most of these deaths can be attributed to hemorrhagic shock. Hemorrhagic shock accounts for 30% of deaths from injury around the world in 2012. Its mortality ranges from 36.5% to 69%. Hemorrhagic shock is a clinical syndrome resulting from circulatory dysfunction that leads to decreased tissue perfusion, the accumulation of oxygen debt, and ultimately to multiple organ injury and death if left untreated, so appropriate management and treatment are necessary to prevent adverse events and outcomes. The intestine is affected early in the process of shock since cardiac output is redirected to so called vital organs like the heart, brain and kidneys, which leads to a reduced perfusion of the intestine. One of the early events in intestinal injury is the loss of the intestinal epithelial barrier integrity. The later is a well-recognized medical consequence of a wide range of life-threatening stress conditions, such as hemorrhagic shock, trauma, burn injury and septic shock. Even milder stress conditions, such as prolonged endurance exercise and chronic psychological stress can induce intestinal barrier dysfunction. Intestinal mucosal barrier consists of a monolayer of epithelial cells, covered by a mucus layer underlined by numerous immune cells present in the lamina propria, and is essential for maintenance of intestinal homeostasis and host health. The barrier is regulated by intercellular apical junctional complex (AJC) of proteins, which permits passive entry of nutrients, ions, and water and restricts paracellular permeability of allergens, bacteria and their products such as endotoxins and peptidoglycans. The AJC consists of tight junctions (TJs) and its subjacent adherens junctions (AJs), which seal the space between epithelial cells. The TJs are composed of transmembrane proteins including occludin and claudin family and interact with cytoplasmic plaque proteins such as zonula Occludens family. Zona occludens link the TJs and AJs to cytoskeletal proteins and thereby resulting in stabilization of apical junctions dynamics. |