V_A对V_E抗辐射自由基损伤作用中的剂量效应关系
|
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。
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 .
71
Those 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, which
suggested 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.
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。
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 .
71
Those 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, which
suggested 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.
引文
1. Fisher BJ et al. Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant systemic therapy alone: patterns of recurrence. Int J Radiat Oncol Biol Phys, 1997 Jun, 38:3,541-50
2．海春旭．抗氧化剂协同作用与祛斑类中药新药研究．生命科学与生物技术(中国科协第三届青年学术年会论文集) 中国科学技术出版，1998：324-327。
3．夏寿萱主编．分子放射生物学．北京：原子能出版社，1992：28-38。
4. Halliwell B, Gutteridge J MC.Free Radicals in Biology and Medicine. New York:Oxord University Press, 1985:42
5. Inouye B, Aono K, Irda S et al.Influence of superoxide system,vitamin E, and superoxide dismutase on radiation consequences.Physical Chem Phys, 1979;11:151
6. Petkau A, Kelly, Chelack WS et al. Radioprotection of mice by superoxide dismutase. Biophys Res Commun, 1975;65:886
7. Tappel A L:Vitam Horm N Y. 1962;20:492.
8．侯悦主编．军队卫生学．北京：人民卫生出版社1998：4：246
9. Glass WA, Varma MN. Physical and Chemical Mechanisms in Molecular Radiation Biology.New York:Plenum Press, 1991:28-46
10. Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and assay for superoxide dismutase. Archives of Biochemistry and Biophysics 1978;186:189-195.
11. Yisun et al:Free Rad Res Comus 1988;4:299-309.
13. Aebl H.Catalase.In:Enzyme Activities-oxidoreduc tases.1983:673-683.
14．周捷、李陪成．血清维生素A和维生素E的微量荧光测定法．中华医学检验杂志．1989，12(6)：346～347
验杂志．1989，12(6)：346～347
15. Bradford MM.A rapide and sensitive methed for the quantitation of microgram quantities of protein utilizing the principle of proteindye buiding. Anal Bioch 1976;72:248.
12．王德文、李延平、刘雪桐．2.5-2100戈瑞大鼠的辐射效应．中华放射与防护杂志．1984；4(1)：17-19
16．刘芬菊、江家贵、易剑等．外源性的SOD减轻大剂量的照射对小鼠的损伤效应．苏州医学院学报．1999；19(7)：765-766
17．赵厚安、方允中．整体照射对小鼠肝、脾亚细胞各部分中锰-超氧化物歧化酶及铜锌-超氧化物歧化酶活力的影响．生物化学与生物物理学报1989；21(3)：195-199
18．邹仲敏、孙慧勤、罗成基．66y γ射线照射诱导骨髓造血细胞凋亡．中华放射医学与防护杂志．1998：18(6)：314-316
19．崔玉芳、高亚兵、杨红等．辐射引起小鼠外周血淋巴细胞凋亡及其机理．细胞与分子免疫学杂志．1998；14(4)：278-281
20．封江彬、王秀娥、常世琴．6.00Gy γ射线照射后大鼠血小板聚集功能的变化．中华放射医学与防护杂志．1999：19(3)：204-205
21．王荣先、张荷清、杨秀梅等．天然胡萝卜素对辐射小鼠提升血细胞作用的研究．中国辐射卫生．1998：(7)：40-41
22．黄克维、吴丽娟主编．临床神经病理学．北京：人民军医出版社．1999：1-7
23．卫生部卫生监督司．保健食品功能学评价程序和检验方法．1996：23-34
24. Schulthesis TE, Kun LE, Ang KK, et al. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys, 1995,31:1093-1112
24．(美)E．J霍尔著．放射生物学．北京：原子能出版社．117-118
25．Ed and Kaizhi Shaman美国加州大学尔湾分校医学院医疗系营养素和长寿自由基生命科学进展1998；6：36-47
26. Marzatico F, Gaetani P, Tartara F et al. Antioxidant status and
alphal-antiproteinase activity in subarachnoid hemorrhage patients. Life Sci. 1998; 63(10) : 821-6
27． Niki E, Noguchi N, Tsuchihashi H et al, Interaction among vitamin C, vitamin E, and beta-carotene. Am J Clin Nutr. 1 99512;62 (6Suppl) 1322S-1326S
28． Olson JA et al. Molecular actions of carotenoids. Ann N Y Acad Sci, 1993;691:156-166
29． Stal 0 Dufmats M Hatschek T et al. S-phase fraction is a prognostic factor in stage I breast carcinoma. Ann N Y Sci.1993;691:10-19
30． Liebler DC. Antioxidant reactions of carotenoids. Ann N Y Acad Sci, 1993;691:20-31
31． Yamanushi T, Igarashi 0． The mobilization and tissue distribution of beta-carotene in the rat by the venous injection method. J Nutr Sci Vitaminol Tokyo. 1995 Apr;41(2) :169-77
32． Calzada C, Bruckdorfer KR, Rice Evans CA. The influence of antioxidant nutrients on platelet function in healthy volunteers. Atherosclerosis. 1997 Jan 3; 128(1) : 97-105
33． Tsuchihashi H,KigoshiM, IwatsukiM et al, Action of beta-carotene as an antioxidant against lipid peroxidation. Arch-Biochem-Biophys. 1995 Oct 20; 323(1) : 137-47
34． Canfield LM Valenzuela JG. Ann N Y Acad Sci, Cooxidations: significance to carotenoid action in vivo. 1993;691:Preface
35． Palozza P, Calviello G, Bartoli GM. Prooxidant activity of beta-carotene under 100% oxygen pressure in rat liver microsomes. Free Radic Biol Med. 1995 Dec; 19(6) : 887-92
36． Bohm F, Edge R, McGarvey DJ. Beta-carotene with vitamins E and C offers synergistic cell protection against NOx. FEBS Lett. 1998 Oct 9; 436(3) : 387-9
37． 海春旭.自由基与自由基清除剂相互作用及对肿瘤细胞周期癌基因及其
表达的调空．第四军医大学博士学术论文95．6
38. Tesoriere L, Bongiorno A Re R, Livrea MA.Reciprocal protective effects of all-trans retinol and alpha-tocopherol during lipid peroxidation in retinal membranes. Biochem Mol Biol Int. 1995 Sep;37(1): 1-7
39. Alam BS… Nutr Cancer. 1990,14(2) 111-116
40．周珉、陈瑗．脂质过氧化作用及其在辐射损伤中的意义．第一军医大学学报．1993．12(增刊)：385-398
41. Konings AWT, Drijuer EB. Radiation effects on memberanes:Ⅰ.Vitamin dificiency and lipid peroxidation.Radiat Res, 1979;80(3):494
42. Alper T: "Biophysical Aspeets of Radiation Quality" Proc Symp Lueas Height IAEA,Viennap.171,197113. Alper T:brit J Radrol 47:240,1974
43. Kong S et al. The role of interaction between O_2, H_2O_2,OH, e-and O_2~- in free medical damage to biological system.Arch Biochan Bioohys. 1980,204-218.
44．孙存普、张建中、段绍瑾．自由基生物学导论．中国科技大学出版社：1999；194-202
45．辛淮生、付海珍、柳春华等．维生素E、C对紫外线辐射致皮肤细胞氧化性损伤的保护作用．镇江医学院学报．1998：8(4)：445-446
46．韩光、饶俐俐．紫外线照射下小鼠皮肤总抗氧化能力变化的观察．赣南医学院学报．1997；17(1)：5-6
47. Pekau A,Chelack WS.Radioprotective effect of superoxide dismutase on model phspholipid membranes.Biochim Biophys Acta,1976;433:445
48. Inouye B, Aono K, Irda S et al. Influence of superoxide system,vitamin E, and superoxide dismutase on radiation consequences.Physical Chem Phys, 1979;11:151
49. Petkau A, Kelly K, Chelack WS .Pleskach SD. Protective effect of superoxide dismutase on erythrocytes of X-irradiated mice. Int J Radiat Bio1,1976;29:297
50．方允中、李文杰主编．自由基与酶．北京：科学出版社，1989：1-11
51．张君岚、关启翔、黄善生．不同剂量紫外线照射对血液抗氧化作用的影响．中华物理医学杂志．1996．03．25；18(1)：47-49
52. White, J.R. et al.,Superoxide radical in the mechanism of action of strponigrin. Fed. Proc, 1971,30:1147
53. Purohit, S.C. et al. Structural modification on human erythrocyte mebranes following gamma irradiation.Int. J. Radiat. Biol. 1980,38,147
54．陈静、刘基芳、张晓刚．放疗对癌症患者体内抗氧化剂含量的影响．白求恩医科大学学报．1996：22(3)：267-269
55．田晓华．氧化应激与抗氧化维生素的作用．国外医学卫生学分册1996；23(4)229-233
56. Beltantone R, et al. Whole live intraoperative irradiation after partial hepatectomy produced minimal functional and pathological lesions. J Surg Oncol,1992;52(2):81
57. Cicciarello R, d'Avella D, Gagiardi ME, et al. Time-related ultrastructural changes in an experimental model of whole brain irradiation. Neurosurgery, 1996,38:772.
58. Yamaguchi N, Yamashima T, Yamashita J. A histological and flow cytometric study of dog brain endothelial cell injuries in delayed radiation necrosis. J Neurosurg, 1991,74:625
59. Schulthesis TE, Kun LE, Ang KK, et al. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys, 1995,31:1093.
60．田野、包仕尧、刘春风等．大鼠大脑照射后海马区细胞凋亡与病理形态学变化的研究．中华创伤杂志．2000，20(2)：84-86
61．张剑宁、章翔、易声禹等．微波辐射对海马CA-1区神经元的损害及其防治．中华神经外科杂志．1999：15(1)：14-16
62．杜泽吉、苏燎原、孙国器．辐射研究与辐射工艺学报．1994，12(1)：26-29
63. Goodman GE, Metch BJ,Omenn GS.The effect of long-term beta-carotene and vitamin A administration on serum concentrations of alpha-tocopherol. Cancer Epidemiol 8iomarkers Prey. 1994 Jul Aug;3(5): 429-32
64. Myers DK, Chetty KG. Effect of radiosensitizing agents on DNA strand breaks and their rapid repair during irradiation. Radiat Res.1973 Feb; 53(2): 307-14
65. Maggis B, et al:Biochem J 161:111,1977
67. Krshoff BH, et al:Cancer Lett 5(3):123,1978
68．刘学成、于伯勇、高声伟等．α-生育酚对受照小鼠的保护作用的实验研究．中华放射医学与防护杂志．1990：10(1)：60
69．倪庆桂、裴云．β-胡萝卜素对~(60)CO-γ射线诱发的大鼠T-淋巴细胞次黄嘌呤-鸟嘌呤磷酸核糖转移酶位点突变影响．中国药理学报．1997，18(6)：535-536
70. Lynch SM,Morrow JD,Roberts LJ 2nd et al.Formation of non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in plasma and low density lipoprotein exposed to oxidative stress in vitro. J-Clin-Invest. 1994 Mar; 93(3): 998-1004
71. Leibovitz B, Hu ML, Tappel AL. Dietary supplements of vitamin E,beta-carotene, coenzyme Q10 and selenium protect tissues against lipid peroxidation in rat tissue slices. J Nutr. 1990 Jan; 120(1):97-104
72. Blot WJ, Li JY, Taylor PR et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population [see comments]. J Natl Cancer Inst. 1993 Sep15; 85(18): 1483-92
73． Wang XD, Andersson R, Soltesz V etal. Phospholipids prevent enteric bacterial translocation in the early stage of experimental acute liver failure in the rat. Scand J Gastroenterol. 1994 Dec; 29(12) : 1117-21
2．海春旭．抗氧化剂协同作用与祛斑类中药新药研究．生命科学与生物技术(中国科协第三届青年学术年会论文集) 中国科学技术出版，1998：324-327。
3．夏寿萱主编．分子放射生物学．北京：原子能出版社，1992：28-38。
4. Halliwell B, Gutteridge J MC.Free Radicals in Biology and Medicine. New York:Oxord University Press, 1985:42
5. Inouye B, Aono K, Irda S et al.Influence of superoxide system,vitamin E, and superoxide dismutase on radiation consequences.Physical Chem Phys, 1979;11:151
6. Petkau A, Kelly, Chelack WS et al. Radioprotection of mice by superoxide dismutase. Biophys Res Commun, 1975;65:886
7. Tappel A L:Vitam Horm N Y. 1962;20:492.
8．侯悦主编．军队卫生学．北京：人民卫生出版社1998：4：246
9. Glass WA, Varma MN. Physical and Chemical Mechanisms in Molecular Radiation Biology.New York:Plenum Press, 1991:28-46
10. Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and assay for superoxide dismutase. Archives of Biochemistry and Biophysics 1978;186:189-195.
11. Yisun et al:Free Rad Res Comus 1988;4:299-309.
13. Aebl H.Catalase.In:Enzyme Activities-oxidoreduc tases.1983:673-683.
14．周捷、李陪成．血清维生素A和维生素E的微量荧光测定法．中华医学检验杂志．1989，12(6)：346～347
验杂志．1989，12(6)：346～347
15. Bradford MM.A rapide and sensitive methed for the quantitation of microgram quantities of protein utilizing the principle of proteindye buiding. Anal Bioch 1976;72:248.
12．王德文、李延平、刘雪桐．2.5-2100戈瑞大鼠的辐射效应．中华放射与防护杂志．1984；4(1)：17-19
16．刘芬菊、江家贵、易剑等．外源性的SOD减轻大剂量的照射对小鼠的损伤效应．苏州医学院学报．1999；19(7)：765-766
17．赵厚安、方允中．整体照射对小鼠肝、脾亚细胞各部分中锰-超氧化物歧化酶及铜锌-超氧化物歧化酶活力的影响．生物化学与生物物理学报1989；21(3)：195-199
18．邹仲敏、孙慧勤、罗成基．66y γ射线照射诱导骨髓造血细胞凋亡．中华放射医学与防护杂志．1998：18(6)：314-316
19．崔玉芳、高亚兵、杨红等．辐射引起小鼠外周血淋巴细胞凋亡及其机理．细胞与分子免疫学杂志．1998；14(4)：278-281
20．封江彬、王秀娥、常世琴．6.00Gy γ射线照射后大鼠血小板聚集功能的变化．中华放射医学与防护杂志．1999：19(3)：204-205
21．王荣先、张荷清、杨秀梅等．天然胡萝卜素对辐射小鼠提升血细胞作用的研究．中国辐射卫生．1998：(7)：40-41
22．黄克维、吴丽娟主编．临床神经病理学．北京：人民军医出版社．1999：1-7
23．卫生部卫生监督司．保健食品功能学评价程序和检验方法．1996：23-34
24. Schulthesis TE, Kun LE, Ang KK, et al. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys, 1995,31:1093-1112
24．(美)E．J霍尔著．放射生物学．北京：原子能出版社．117-118
25．Ed and Kaizhi Shaman美国加州大学尔湾分校医学院医疗系营养素和长寿自由基生命科学进展1998；6：36-47
26. Marzatico F, Gaetani P, Tartara F et al. Antioxidant status and
alphal-antiproteinase activity in subarachnoid hemorrhage patients. Life Sci. 1998; 63(10) : 821-6
27． Niki E, Noguchi N, Tsuchihashi H et al, Interaction among vitamin C, vitamin E, and beta-carotene. Am J Clin Nutr. 1 99512;62 (6Suppl) 1322S-1326S
28． Olson JA et al. Molecular actions of carotenoids. Ann N Y Acad Sci, 1993;691:156-166
29． Stal 0 Dufmats M Hatschek T et al. S-phase fraction is a prognostic factor in stage I breast carcinoma. Ann N Y Sci.1993;691:10-19
30． Liebler DC. Antioxidant reactions of carotenoids. Ann N Y Acad Sci, 1993;691:20-31
31． Yamanushi T, Igarashi 0． The mobilization and tissue distribution of beta-carotene in the rat by the venous injection method. J Nutr Sci Vitaminol Tokyo. 1995 Apr;41(2) :169-77
32． Calzada C, Bruckdorfer KR, Rice Evans CA. The influence of antioxidant nutrients on platelet function in healthy volunteers. Atherosclerosis. 1997 Jan 3; 128(1) : 97-105
33． Tsuchihashi H,KigoshiM, IwatsukiM et al, Action of beta-carotene as an antioxidant against lipid peroxidation. Arch-Biochem-Biophys. 1995 Oct 20; 323(1) : 137-47
34． Canfield LM Valenzuela JG. Ann N Y Acad Sci, Cooxidations: significance to carotenoid action in vivo. 1993;691:Preface
35． Palozza P, Calviello G, Bartoli GM. Prooxidant activity of beta-carotene under 100% oxygen pressure in rat liver microsomes. Free Radic Biol Med. 1995 Dec; 19(6) : 887-92
36． Bohm F, Edge R, McGarvey DJ. Beta-carotene with vitamins E and C offers synergistic cell protection against NOx. FEBS Lett. 1998 Oct 9; 436(3) : 387-9
37． 海春旭.自由基与自由基清除剂相互作用及对肿瘤细胞周期癌基因及其
表达的调空．第四军医大学博士学术论文95．6
38. Tesoriere L, Bongiorno A Re R, Livrea MA.Reciprocal protective effects of all-trans retinol and alpha-tocopherol during lipid peroxidation in retinal membranes. Biochem Mol Biol Int. 1995 Sep;37(1): 1-7
39. Alam BS… Nutr Cancer. 1990,14(2) 111-116
40．周珉、陈瑗．脂质过氧化作用及其在辐射损伤中的意义．第一军医大学学报．1993．12(增刊)：385-398
41. Konings AWT, Drijuer EB. Radiation effects on memberanes:Ⅰ.Vitamin dificiency and lipid peroxidation.Radiat Res, 1979;80(3):494
42. Alper T: "Biophysical Aspeets of Radiation Quality" Proc Symp Lueas Height IAEA,Viennap.171,197113. Alper T:brit J Radrol 47:240,1974
43. Kong S et al. The role of interaction between O_2, H_2O_2,OH, e-and O_2~- in free medical damage to biological system.Arch Biochan Bioohys. 1980,204-218.
44．孙存普、张建中、段绍瑾．自由基生物学导论．中国科技大学出版社：1999；194-202
45．辛淮生、付海珍、柳春华等．维生素E、C对紫外线辐射致皮肤细胞氧化性损伤的保护作用．镇江医学院学报．1998：8(4)：445-446
46．韩光、饶俐俐．紫外线照射下小鼠皮肤总抗氧化能力变化的观察．赣南医学院学报．1997；17(1)：5-6
47. Pekau A,Chelack WS.Radioprotective effect of superoxide dismutase on model phspholipid membranes.Biochim Biophys Acta,1976;433:445
48. Inouye B, Aono K, Irda S et al. Influence of superoxide system,vitamin E, and superoxide dismutase on radiation consequences.Physical Chem Phys, 1979;11:151
49. Petkau A, Kelly K, Chelack WS .Pleskach SD. Protective effect of superoxide dismutase on erythrocytes of X-irradiated mice. Int J Radiat Bio1,1976;29:297
50．方允中、李文杰主编．自由基与酶．北京：科学出版社，1989：1-11
51．张君岚、关启翔、黄善生．不同剂量紫外线照射对血液抗氧化作用的影响．中华物理医学杂志．1996．03．25；18(1)：47-49
52. White, J.R. et al.,Superoxide radical in the mechanism of action of strponigrin. Fed. Proc, 1971,30:1147
53. Purohit, S.C. et al. Structural modification on human erythrocyte mebranes following gamma irradiation.Int. J. Radiat. Biol. 1980,38,147
54．陈静、刘基芳、张晓刚．放疗对癌症患者体内抗氧化剂含量的影响．白求恩医科大学学报．1996：22(3)：267-269
55．田晓华．氧化应激与抗氧化维生素的作用．国外医学卫生学分册1996；23(4)229-233
56. Beltantone R, et al. Whole live intraoperative irradiation after partial hepatectomy produced minimal functional and pathological lesions. J Surg Oncol,1992;52(2):81
57. Cicciarello R, d'Avella D, Gagiardi ME, et al. Time-related ultrastructural changes in an experimental model of whole brain irradiation. Neurosurgery, 1996,38:772.
58. Yamaguchi N, Yamashima T, Yamashita J. A histological and flow cytometric study of dog brain endothelial cell injuries in delayed radiation necrosis. J Neurosurg, 1991,74:625
59. Schulthesis TE, Kun LE, Ang KK, et al. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys, 1995,31:1093.
60．田野、包仕尧、刘春风等．大鼠大脑照射后海马区细胞凋亡与病理形态学变化的研究．中华创伤杂志．2000，20(2)：84-86
61．张剑宁、章翔、易声禹等．微波辐射对海马CA-1区神经元的损害及其防治．中华神经外科杂志．1999：15(1)：14-16
62．杜泽吉、苏燎原、孙国器．辐射研究与辐射工艺学报．1994，12(1)：26-29
63. Goodman GE, Metch BJ,Omenn GS.The effect of long-term beta-carotene and vitamin A administration on serum concentrations of alpha-tocopherol. Cancer Epidemiol 8iomarkers Prey. 1994 Jul Aug;3(5): 429-32
64. Myers DK, Chetty KG. Effect of radiosensitizing agents on DNA strand breaks and their rapid repair during irradiation. Radiat Res.1973 Feb; 53(2): 307-14
65. Maggis B, et al:Biochem J 161:111,1977
67. Krshoff BH, et al:Cancer Lett 5(3):123,1978
68．刘学成、于伯勇、高声伟等．α-生育酚对受照小鼠的保护作用的实验研究．中华放射医学与防护杂志．1990：10(1)：60
69．倪庆桂、裴云．β-胡萝卜素对~(60)CO-γ射线诱发的大鼠T-淋巴细胞次黄嘌呤-鸟嘌呤磷酸核糖转移酶位点突变影响．中国药理学报．1997，18(6)：535-536
70. Lynch SM,Morrow JD,Roberts LJ 2nd et al.Formation of non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in plasma and low density lipoprotein exposed to oxidative stress in vitro. J-Clin-Invest. 1994 Mar; 93(3): 998-1004
71. Leibovitz B, Hu ML, Tappel AL. Dietary supplements of vitamin E,beta-carotene, coenzyme Q10 and selenium protect tissues against lipid peroxidation in rat tissue slices. J Nutr. 1990 Jan; 120(1):97-104
72. Blot WJ, Li JY, Taylor PR et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population [see comments]. J Natl Cancer Inst. 1993 Sep15; 85(18): 1483-92
73． Wang XD, Andersson R, Soltesz V etal. Phospholipids prevent enteric bacterial translocation in the early stage of experimental acute liver failure in the rat. Scand J Gastroenterol. 1994 Dec; 29(12) : 1117-21