LIPID PEROXIDATION IN ALCOHOLIC LIVER DISEASE

目的：探讨酒精性肝病的发病机制，为酒精性肝病的防治提供理论依据。 饮食干预和预防医学将使我们有可能 尽量减少这种疾病。 具体目标：产生类似于酒精性肝病的 人类酒精性肝病包括脂肪变性、炎症、坏死和纤维化 连续灌胃限量饲料和酒精对大鼠肝脏的影响 喂食。这种饮食方案的修改方式是，仅通过改变 一种饮食成分，即脂肪，当大鼠处于 喂了乙醇。产生肌萎缩侧索硬化症的饮食含有25%来自于 从玉米油中提炼出来。预防ALD的饮食用玉米油代替玉米油 牛油(卡路里的25%)。使用这两种节食方案， 产生ALD，而不产生ALD的，将对老鼠进行分析 生化和形态异常的存在，以便识别 哪些异常与ALD有关，哪些与ALD无关。这个 与ALD相关的异常将被认为是可疑的 ALD的发病机制有待进一步研究。预防措施将会 接受测试以确定哪些机制涉及治疗性 干预。有待研究的机制包括：1)能量代谢 活体31P磁共振成像的肝脏与肝脏中的O2张力相关 2)亚油酸/花生四烯酸 代谢产物和抑制剂的GL色谱层析和高效液相色谱研究 花生四烯酸代谢酶；3)伊藤的形态计量学测定 细胞活化与肝纤维化相关的电子学研究 4)酒精诱导的琥珀酸脱氢酶组织化学 3区肝细胞通透性增加；5)维生素A代谢 在ALD。

Objectives: To determine the mechanism of alcoholic liver disease so that dietary interventions and preventive medicine will make it possible to minimize this disease. Specific Aims: To produce alcoholic liver disease which closely resembles human ALD including fatty change, inflammation, necrosis, and fibrosis of the liver in rats fed defined diets and alcohol by continuous intragastric feeding. This dietary regimen is modified in a way that by changing only one dietary ingredient, i.e. fat, no ALD lesion develops when the rats are fed ethanol. The diet which produces ALD contains 25% of calories derived from corn oil. The diet which prevents ALD substitutes corn oil with tallow (25% of calories). Using these two diet regimens, the one that produces ALD and the one that does not, the rats will be analyzed for the presence of biochemical and morphologic abnormalities in order to identify which abnormalities are associated with ALD and which are not. The abnormalities associated with ALD will be considered suspect as involved in the mechanism of ALD and will be studied further. Preventive measures will be tested to determine which mechanisms are involved by therapeutic intervention. Mechanisms to be studied include: 1) energy metabolism of the liver using 31P MRS in vivo correlated with 02 tension in the liver during chronic alcohol feeding; 2) linoleic acid/arachidonic acid metabolism using GL chromatography and HPLC of metabolites and inhibitors of arachidonate metabolizing enzymes; 3) morphometric determination of Ito cell activation associated with liver fibrosis using the electron microscope; 4) succinic dehydrogenase histochemistry for alcohol-induced increased permeability in zone 3 liver cells; and 5) vitamin A metabolism in ALD.