【作者】 王璐；

【导师】 海春旭；

【作者基本信息】 第四军医大学 ， 毒理学， 2001， 硕士

【摘要】 自由基生物学与放射医学是国内外比较活跃的研究领域，辐射损伤的防治是一个尚未解决的难点，人们正通过各种手段寻找解决这个难点的途径。由于辐射可诱发自由基损伤，抗自由基损伤可有效的防治辐射作用。因此，近几年来，辐射与自由基的关系日益受到重视，在对辐射损伤的防护上，人们找到了一条新途径——自由基清除剂。寻找高效抗氧化剂以及如何合理地使用抗氧化剂成为许多实验室研究的重点。 早在1990年，“抗氧化剂复合链”的假说即已提出，并通过实验室的大量工作得到进一步证实。这一学说的主要内容为：在生物体内，自由基反应与脂质过氧化损伤高度相关、连锁，单一的自由基清除剂或抗氧化剂作用有限，而由具有不同的脂/水溶性，不同分子量，不同作用位点，不同存在部位；带有不同电荷组成的“复合自由基清除剂”的机体防御体系，具有高效消除自由基损伤的作用。在此理论指导下，我们对抗氧化剂V_A、V_E在抗氧化作用的协同和互补作用及剂量效应关系进行了研究，以期为抗氧化剂的联合应用提供实验依据。 研究表明：自由基清除剂或抗氧化剂能够有效地干预或减轻辐射损伤的效应。辐射损伤诱发的自由基反应，同其它自由基反应一样，也是链式连锁放大反应。单一或少数自由基清除剂不能有效阻断这种链式反应，有些外源性抗氧化剂如SOD、GSH等不能进入细胞内，很难发挥有效的清除作用。单独或少数抗氧化剂在实验室研究中效果显著，但用到机体整体时效果不显著，原因之一就是自由基链式反应所致。 最近，国际自由基学会主席L.Packer教授提出了“抗氧化剂网络（antioxidants network）”的新概念，将多功能、多位相复合抗氧化剂，称为抗氧化剂网络，试图解释多年来单独抗氧化剂在整体清除Ros上效果不佳的问题。“抗氧化剂复合链”和“抗氧化剂网络”理论的提出，在指导研究使用多功能、多位相复合抗氧化剂，有效地抑制辐射自由基损伤提供了新的研究思路。因此，研究V_A、V_E在抗辐射中的相互关系，特别是剂量效应关系，是验证相关理论的重要的基础性工作，也是抗辐射损伤的有效途径之一， 第四军医大学硕士研究生论文 共71页 有着极其重要的意义。 我们从以下几方面进行了探讨：1．辐射造成大鼠体内脂质过氧化反应， 从而对机体造成损伤。2．V＾、V。具有抗氧化作用，可以对辐射后的大鼠起保 护作用。3．通过V＾对V。影响的剂量效应关系的研究，试图证明V＾、V。在抗脂 质过氧化的过程中，其作用并不是简单的相互叠加作用，而存在桔抗或消耗 作用。4．从病理学的角度（包括脑、肝、肠HE染色，海马电镜及图象分析） 在施加不同V＾、V。保护因素后，观察大鼠的组织学变化，从而更有力的证实 V。与V＾在抗氧化中的相互关系。 实验结果显示：1、受辐射后大鼠体内的MDA明显升高，动物出现厌食、 恶心、呕吐、腹泻等症状，说明辐射可以使动物产生脂质过氧化反应，从而 造成相应的损害。表明辐射的自由基损伤模型复制是成功的。2、辐射后V＾、 V。的含量降低，说明V。、V。抗氧化作用中均有明显消耗。3、作为细胞自由 基清除剂的SOD在血清中含量升高，说明辐射可以诱导SOD的动员和生成。 4、CAT虽然不直接清除自由基，但是它可以降低细胞中H。0。浓度，辐射使 CAT降低。5、施加保护因素V＾、V。后，各种酶及维生素的含量发生了变化， 他们与阳性组均有显著性差异，说明人、Vs具有抗氧化作用。当二者合用并 在剂量上有一定差异时，V＾消耗V。的作用便明显地表现出来。从组织病理切 片和图象分析上得到证实，表明V＾对V。的消耗存在剂量效应关系。 结果提示：辐射可以引起脂质过氧化反应，对机体造成影响。V＾、V。作 为非酶类的自由基清除剂具有较好的抗氧化作用。二者在合用过程中，V＾ 具有消耗V。的作用，并存在一定的剂量效应依赖性，提示在抗氧化剂联合 应用中，应合理配伍注意联合使用抗氧化剂自身的桔抗作用，同时，单独使 用V＾发挥抗氧化作用时也应注意对体内自身V。的消耗，从而最终影响整体 的抗氧化效果。更多还原

【Abstract】 Free radical biology and radiation medical science are the extremely active studies and research areas. The preventive and treatment of radiation injury are difficult areas which are not still solved. People are seeking for ways to solve them. Recently, more and more attention has been payed to the relations between radiation and free radical. To prevent the radiation damage, people have found a new way to scavenge free radical. Some laboratories focus on effective antioxidants and use them to inhibit peroxidation induced by radiation reasonably.In 1990, the hypothesis of "Multi-antioxidants chain" was raised and then was proved by some laboratories. The basis of theory is: distinct form of antioxidant that to acqure high efficient electric charge, should be one with different warter-solvable or fat-solvable, different molecular weight different staying and action site, different electric change, and that could play an important role on inhibiting reactive oxygen species injury, Accoring the above hypothesis, the aims of this thesis were to demostrate the relationship between vitamin A and vitamin E against oxidative stress and the relation between dosages of VA, VE in order to provide experimental basis for combine ation of antioxidants using .71Those data suggested that reciprocal protective effects between vitamin A and vitamin E might strongly contribute to the defence of membranes against oxidative stress. Radical scavenger or oxidation is a chain-breaking antioxidant that prevents the propagation of free radical damage. A few radical scavengers can not block this chain reaction. Some external antioxidant as SOD, GSH etc. cannot enter the cells, so it is very difficult for them to take an effect.Lately, professor L.Packer, the president of international free radical association, has raised a new concept of "antioxidants network", trying to explain why singal antioxidant can not have a good effect on getting rid of Ros in systematic level of body. It is possible to use antioxidants compound to refrain radiation damage. Therefore, it is very important to study the interaction between vitamin A and vitamin E in anti-radiation and the interrelation between their dosages and effects.In our study, we payed our attention to the following points: 1. Radiation injury style determined through lipid peroxidation in vivo of rat. 2. Vitamin A and vitamin E may strongly contribute to the defence of membranes against oxidative stress. Vitamin A and E represent an important defensive system against free radicals. Particularly, vitamin E acts as an anti-oxidant by scavenging free radicals. 3. Vitamin A consumes Vitmamin E during antilipid peroxidation. 4.Pathological changes obscued during the later phase of protection factor stress.As results we found that MDA significantly rised in rat. Vitamin A and E were reduced after the radiation, whichsuggested those Vitamin A and E both have the function of antioxidation. As a free radical scavenger, the content of SOD rised, which suggested that it could induce increase of some enzyme content when radiated. We also found that the contents of some enzymes and vitamins changed after giving Vitamin A and E. Vitamin A could consume Vitamin E when both of them were used. Thus we concluded that radiation could irratate lipid peroxidation. Vitamin A and E represent an important defensive system against free radicals reactions. Vitamin A consumes Vitmamin E during they are used at the same time. So we must pay attention to using combining medicine.更多还原