GI BARRIER HEAT INJURY--SYSTEMIC & MOLECULAR MECHANISMS

描述(改编自申请人的摘要)： 这一系列研究的目的是澄清 热损伤与热发展过程中的肠道通透性障碍 驯化，以及(氧自由基)的机制 破坏障碍物。作者认为，体温过高会引发 肠缺血与活性氧的产生 这降低了屏障功能，导致内毒素退出 肠腔进入循环，进而产生细胞因子和 导致低血压。他们进一步提出，热休克蛋白 抵消ROS的影响。他们还将确定地点和 热致通透性功能障碍的时间进程。具体的 将要进行的实验涉及研究的不同方面。 1代ROS。他们将在体外测试(细胞培养中的2个菌株 外加一株转MnSOD的菌株，单层电导)和体内 (~(51)Cr-EDTA清除量、门静脉内毒素水平、肿瘤坏死因子、热休克蛋白和诱导型 一氧化氮合酶水平、甘露醇通透性)是否膜 功能因加热引起的ROS升高而改变，由 饮食方式，通过在系统中添加抗氧化剂来减少。 2.热休克蛋白防护。表达升高的热休克蛋白的细胞也将在 上述特性以及习服大鼠的屏障功能。

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.