GI BARRIER HEAT INJURY--SYSTEMIC & MOLECULAR MECHANISMS

胃肠道屏障热损伤——系统性

• 批准号: 6330174
• 负责人: LARRY OBERLEY
• 金额: $ 29.19万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6330174
• 关键词: acclimatization; antioxidants; dietary control; enzyme activity; enzyme induction /repression; free radical oxygen; gastrointestinal absorption /transport; gastrointestinal disorder; gastrointestinal epithelium; gastrointestinal toxin absorption; heat injury; hyperthermia; laboratory rat; lipopolysaccharides; membrane permeability; nitric oxide synthase; nutrition related tag; septic shock; stress proteins; superoxide dismutase; tissue /cell culture; tumor necrosis factor alpha

DESCRIPTION (Adapted from the applicant's abstract): The purpose of this series of studies is to clarify the importance of the gut permeability barrier in the development of heat injury and heat acclimation, and the mechanisms responsible (oxygen free radicals) for damaging the barrier. The authors propose that hyperthermia provokes intestinal ischemia and production of reactive oxygen species (ROS) which decrement barrier function, leading to the exit of LPS from the lumen of the gut into the circulation, in turn, generating cytokines and leading to hypotension. They further propose that heat shock proteins counteract the effect of ROS. They will also determine the location and time course of permeability dysfunction induced by heat. The specific experiments to be carried out address different aspects of the study. 1 Generation of ROS. They will test in vitro (2 strains in cell culture plus a strain transfected with MnSOD, monolayer conductance) and in vivo (51Cr-EDTA clearance, portal vein LPS levels, TNF, and HSP and inducible nitric oxide synthase levels, mannitol permeability) whether membrane function is altered by the elevations in ROS induced by heating, by dietary means and reduced by addition of an antioxidant to the system. 2. HSP protection. Cells expressing elevated HSP will also be tested in the above properties as well as the barrier function of acclimated rats.

描述（改编自申请人摘要）：