Experimental Study On Mechanisms Involved In Intestinal Epithelial Cell Damage Caused By Whole Body Irradiation And Endotoxin Stress

In the normal condition, intestinal stem cells located in crypts can proliferate asymmetrily, and the produced daughter cells migrate up to villus, together with differentiation and maturation, at last shed at the top of the villus. The rapid self-renewing homeostasis is important for intestinal mucosa to maintain the appropriate structure and function. Many agents targeted gastrointestinal mucosa can disturb the regulated self-renewing process, including genotoxic stresses (irradiation, DNA targeted drugs etc) and non-genotoxic stresses (gastrointestinal inflammation, severe trauma, sepsis etc). When nuclear war and nuclear biochemical terrorism attack happen, geno and non-genotoxic agents would cause damage on the wounded simultaneously or sequently one after the other, resulting in the classical combined injury. But these two kinds of damage agents differ in target cells and the activation of signal transduction pathways, which deters us from making clear the mechanism involved in the pathogenesis and development of intestinal combined injury and proposing the effective treatments.Genotoxic agents such as irradiation can lead to the apoptosis of crypt cells in several hours, but very modest damage to the mature cells resided in the villus. When the mouse was exposed to given dose(8-12Gy) WBI (whole body irradiation), parts of crypt cells could undergo cell cycle arrest, apoptosis and necrosis, resulting in the lack of cell sources for the self-renewing of crypt-villus axis and subsequently the collapse of the integrity of intestinal epithelium barrier. Non-genotoxic stresses, such as severe trauma and shock, often target the villus cells directly, leading to the failure of gastrointestinal barrier and the followed infection, which play key roles in initiating the MODS. MODS can be rapidly induced in an ES (Endotoxin stress) animal model established by LPS treatment in mice, and the lower perfusion, reactive oxygen species and pro-inflammatory facotors occurred in the gut lead to the rapid death and shed of villus cells, resulting in the rapid failure of barrier and absorbing...