VITAMIN E/SELENIUM/OXIDATION/PULMONARY ARACHIDONIC ACID

拟议研究的主要目的是阐明 维生素E和硒参与高血压病的本质 花生四烯酸(AA)的酶促氧化调控 环氧合酶和脂氧合酶途径。为了获得更多 对维生素E和维生素E的精确作用机理的认识(S) 硒依赖的抗氧化防御功能，03是 使用了一种模型氧化剂来研究 氧化应激的生化和免疫学后果 在E/Se缺乏的情况下。需要检验的假设是，一个 氧化应激，如在E/Se缺乏状态下发现的那样，可以 扰动酶的活性以及产品的特性 AA级联。这些AA代谢物可能起着重要的作用 在氧化剂所致肺损伤的病理生理学方面。 因此，我们建议研究臭氧暴露的影响。 在E缺乏、Se缺乏或两者都缺乏的大鼠中：1) 肺组织中过氧化脂质和其他TBA反应产物的水平 2)血栓素A2-前列环素I2的状态 3)前列腺素的形成、F2α、E_2和 D2，以及参与其生物合成的酶，在这种情况下， 谷胱甘肽S转移酶；4)白三烯和 参与其生物合成的酶，特别是5- 脂氧合酶和谷胱甘肽S转移酶；5)能力 肺组织体外代谢花生四烯酸；6)潜力 为AA依赖的脂质过氧化和共氧化 肺和肺泡的苯并-7，8-二氢二醇 巨噬细胞的功能。拟采用的研究方法 包括分光光度和同位素分析 液体酶活性的测定、放射免疫分析 闪烁光谱、GC/MS、薄层和高压 脂层析技术在药物分析中的应用 前列腺素和白三烯。将获得新的信息 从提出的努力中应该加深我们对 维生素E和硒在调节机体功能中的作用 环氧合酶和脂氧合酶途径。

The primary objective of the proposed research is to elucidate the nature of involvement of vitamin E and selenium in the modulation of enzymatic oxidation of arachidonic acid (AA) via the cyclooxygenase and lipoxygenase pathways. To gain further knowledge on the precise mechanism(s) of vitamin E and selenium-dependent antioxidant defense functions, 03 is employed an a model oxidant for the investigation of the biochemical and immunological consequences of oxidant stress under E/Se deficiency. The hypothesis to be tested is that an oxidant stress, such as that found in the E/Se deficient state, can perturb enzyme activities as well as the product profile of the AA cascade. These AA metabolites may play an important role in the pathophysiology of oxidant-induced lung damage. Accordingly, we propose to examine the effects of O3 exposure in rats under E deficiency, Se deficiency or both on: 1) the levels of lipid peroxides and other TBA reactive products in lung and blood; 2) the status of thromboxane A2-prostacyclin I2 homeostatis; 3) the formation of prostaglandins, F2 alpha, E2 and D2, and the enzymes involved in their biosynthesis, in this case, the glutathione S-transferases; 4) the leukotrienes and the enzymes involved in their biosynthesis, particularly the 5- lipoxygenase and the glutathione S-transferases; 5) the capacity of lung to metabolize arachidonic acid in vitro; 6) the potential for AA-dependent lipid peroxidation and cooxidation of benzopyrene-7, 8-dihydrodiol of lung and 7) pulmonary alveolar macrophage functions. The research methods to be employed include spectrophotometric and isotopic assays for the measurement of enzyme activities, radioimmunoassays, liquid scintillation spectrometry, GC/MS, thin-layer, and high pressure lipid-chromatographic techniques for the analysis of prostaglandins and leukotrienes. New information to be derived from the proposed effort should deepen our understanding of the role of vitamin E and selenium in modulation of the cyclooxygenase and lipooxygenase pathways.