GI BARRIER HEAT INJURY--SYSTEMIC & MOLECULAR MECHANISMS

描述（改编自申请人摘要）： 这一系列研究的目的是阐明以下方面的重要性： 肠通透性屏障在热损伤和热损伤中的作用 适应，以及负责的机制（氧自由基） 破坏屏障。作者提出，体温过高会引起 肠缺血和活性氧（ROS）的产生 这减少了屏障功能，导致LPS从 肠腔进入循环，反过来，产生细胞因子， 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， 热诱导的渗透性功能障碍的时间过程。具体 将进行的实验涉及研究的不同方面。 1 ROS的产生他们将在体外进行测试（细胞培养物中的2个菌株 加上用MnSOD转染的菌株，单层电导）和体内 （51Cr-EDTA清除率、门静脉LPS水平、TNF和HSP以及诱导 一氧化氮合酶水平，甘露醇渗透性）是否膜 功能被加热引起的ROS升高改变， 饮食手段和减少添加抗氧化剂的系统。 2. HSP保护表达升高的HSP的细胞也将在 上述性质以及驯化大鼠的屏障功能。

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.