多肽类辐射防护药物应用的研究进展

近年来,核能与核技术在工业、医药、科技、军事等领域的广泛应用使人们暴露于辐射的风险增加,而临床上仍缺乏安全、高效的辐射防护药物。功能多肽在体内担负着重要的调节功能,且多肽类药物具有靶向性、高特异活性、药品安全性高、易于改造修饰等优势。因此,多肽类辐射防护药物的相关研究较多。笔者将对多肽类辐射防护药物的特性和设计思路及其应用进行综述,旨在为多肽类辐射防护药物的研究奠定基础。     

褪黑素在辐射防护中的研究进展

目的为寻找新一代的高效低毒的辐射防护药物奠定基础。方法褪黑素（N-乙酰基-5-甲氧基色胺）是脑松果体的主要分泌物质,具有多项生理功能,如促进睡眠、调节时差、抗衰老、调节免疫、抗辐射等。本文主要对褪黑素在辐射防护中的研究做一个综述,并展望其研究前景。结果褪黑素在临床上具有良好的前景。结论随着科学技术的发展,人们受到辐射的机会越来越多,辐射对健康的影响开始引起了人们的重视,采用药物来提高机体对辐射的抵抗能力是一种积极有效的方法。     

蜂蜜对辐射损伤小鼠保护作用的研究

随着放疗技术的研究和发展,放疗已成为治疗肿瘤的一种重要方法,但其对人体正常组织的损伤不可避免且日益受到重视。因此,辐射防护剂的研究尤为重要。细胞因子、免疫调节剂和常用的含硫化合物等辐射防护剂,由于其有效范围窄、稳定性差、有效时间 短、不良反应大等原因阻碍了其自身的应用,寻找有效范围广、有效时间长、不良反应小的辐射防护剂成为抗辐射药物研究的主要方向。     

小分子辐射防护药物的研究进展

辐射防护药物能减少辐射损伤，促进损伤恢复，与细胞因子等大分子药物相比，小分子辐射防护药使用方便，没有潜在的免疫原风险。笔者汇总了硫醇类化合物、天然抗氧化剂、氮氧自由基、血管紧张素转化酶抑制剂等几类不同的辐射防护药物，对其辐射防护效果以及作用机制进行了总结、归纳，并对此类药物的研发前景进行了展望，旨在为辐射防护药物的进一步研发提供思路。     

补中益气丸等中成药的辐射防护作用

辐射防护药的基本含义是受电离辐射作用前应用能够减轻辐射损伤的药物。1949年开始对其研究之后辐射防护药广泛应用于医学临床、太空、核恐怖及军事上。但是到目前为止，仅WR-2721通过美国食品与药品管理局（FDA）作为临床药物，而VCR-2721在其有效剂量范围之内的毒性问题又严重限制了它的应用，因此安全有效的辐射防护药仍需继续研究。     

四种抗放药对组织氧张力的影响

近年来由于对抗放药物药理作用研究的逐步深入,使我们有可能正确认识药物在机体内所引起的一系列动态变化。进一步的研究证明,这些动态变化构成了药物辐射防护作用的物质基础,而且经常是和其辐射防护作用伴随发生,决定药物效价的大小。因此在     

低、中能X射线吸收剂量测量中的几个问题

辐射防护剂又称抗辐射药物 ,其研究在 6 0年代后期达到高峰 ,但由于高效、低毒 ,可供临床应用的辐射防护剂较难发现 ,从而对辐射防护剂的期望逐渐淡薄起来 ,70年代明显下降。近年来随着肿瘤放疗的进展及核工业的迅速发展 ,国内外对辐射防护剂的研究热情重新高涨 ,主要表现在整体水平、细胞水平、分子水平、基因水平 4个层次对抗辐射药物作用机理进行深入研究 ;有目的寻找毒性低、疗效高的抗辐射新药 ;重视抗放药物的临床应用 (放疗及其他疾病 )及伍用。细胞因子是当今辐射防护剂的研究热点 ,氨巯基化合物仍是研究中的重要化合物类型 ,其他辐…     

淋巴细胞转化试验作为抗放药效价推理的一个手段

在辐射防护药物研究中,如何推断动物实验有效的药物对人体急性放射损伤的防护是否有效,至今是一个尚未解决的课题。曾经进行了多种途径的探讨,如观察药物对肿瘤放疗病人的放射损伤的保护,用人的离体细胞培养试验观察药物对细胞的直接保护作用等,都从不同的侧面说明了一定的问题。但仍不够完善。有必要开展更多方面的工作,为抗放药物的人体效价推理提供更为充分的     

辐射防护基因治疗现状与展望

放射治疗是恶性肿瘤的主要治疗手段之一,超过50%的肿瘤患者在病程的不同阶段都需要接受放疗。尽管影像引导靶向治疗技术不断发展,使患者受到的辐射剂量大大降低,但仍然存在严重的不良反应——正常组织细胞的辐射损伤。为了减少正常组织损伤,研究人员一直在寻找辐射防护的新方法。目前的辐射防护方法多是采用化学合成小分子物质及天然植物提取物作为辐射防护剂使用,但疗效并不十分理想,研究人员迫切想找到一种高效可行的辐射防护新方法。基因治疗以其靶向明确、细胞毒性小、不良反应少等优点在增强细胞和组织相关性能上具有很大优势,使其成为极好的辐射防护新方法。笔者对辐射防护的基因治疗研究及其未来的改进方向做一综述。     

辐射防护剂

辐射防护剂又称“抗辐射药物”,本来是指照射前使用对电离辐射损伤有一定程度预防作用的药物。但随着研究工作的发展,其内容已经扩大到包括照射后早期使用的有效治疗药物。但现有辐射防护剂还不能完全防止损伤的发生,而只能在某种程度上减轻这种损伤。如与其它治疗措施结合应用,能大辐度提高治疗效果,甚至可使放射损伤减轻到亚临床水平或仅出现轻微症状。     

蜂产品对放射性损伤的防治研究进展

在军事、医疗和公共卫生方面,辐射暴露是一个持续而严重的威胁。针对辐射引起的损伤需要有效的预防或缓解治疗,但是目前这些问题尚未得到解决。临床上少数食品药品监督管理局（FDA）批准的辐射防护剂副作用大,限制其广泛使用。据报道,一些天然的无毒化合物（如蜂产品）可通过减轻辐射引起的氧化应激、细胞凋亡和DNA损伤来预防和治疗辐射引起的口腔黏膜炎、食管炎、皮肤损伤、肝损伤、肠道损伤和造血系统的损伤等。这表明这些蜂产品有作为辐射防护剂的潜力。本文就蜂产品对防治放射性损伤的实验及临床研究进行综述。     

Advances in Radioprotection through the Use of Combined Agent Regimens

Summary

The most effective radioprotective agents exhibit toxicities that can limit their usefulness. It may be possible to use combinations of agents with different radioprotective mechanisms of action at less toxic doses, or to reduce the toxicity of the major protective compound by adding another agent. With regard to the latter possibility, improved radioprotection and reduced lethal toxicity of the phosphorothioate WR-2721 was observed when it was administered in combination with metals (selenium, zinc or copper). The known mechanisms of action of potential radioprotective agents and varying effects of different doses and times of administration in relation to radiation exposure must be considered when using combined-agent regimens. A number of receptor-mediated protectors and other biological compounds, including endotoxin, eicosanoids and cytokines, have at least an additive effect when administered with thiol protectors. Eicosanoids and other bioactive lipids must be administered before radiation exposure, whereas some immunomodulators have activity when administered either before or after radiation exposure. For example, the cytokine interleukin-1 administered simultaneously with WR-2721 before irradiation or after irradiation enhances the radioprotective efficacy of WR-2721. The most effective single agents or combinations of protectors result in a decrement in locomotor activity, an index of behavioral toxicity. Recent evidence indicates that administration of the CNS stimulant caffeine mitigates the behavioral toxicity of an effective radioprotective dose of the phosphorothioate WR-3689 without altering its radioprotective efficacy. These examples indicate that the use of combinations of agents is a promising approach for maximizing radioprotection with minimal adverse effects.     

一例职业性放射性皮肤癌的诊断与劳动能力鉴定

当今电离辐射已成为威胁人类健康的重要因素,探索有效的防护策略是放射医学领域研究的重要课题。及时使用辐射防护剂是减少电离辐射对机体正常组织损害最直接有效的方法,大量基于清除自由基、增强DNA损伤修复、诱导辐照组织缺氧及旁效应阻滞等机制的新型辐射防护剂逐渐被开发。本文总结了近年来国内外研究报道的多种辐射防护剂及其潜在的分子生物学机制,为探索新型电离辐射医学防护制剂提供理论参考。     

Effect of cancer chemotherapeutic drugs on the radiation-induced skin reactions in mouse feet

The interactions of seven cancer chemotherapeutic drugs and radiation in normal skin were studied using the mouse foot skin scoring system. Single drug doses were administered 15 min before graded single doses of irradiation or at different intervals before and after a fixed radiation dose. Adriamycin (ADM), bleomycin (BLM), methotrexate (MTX), mitomycin-C (MM-C), and cis-platinum (cis-DDP) all significantly enhanced the radiation-induced skin reactions. The dose-effect factors (DEF) for these drugs ranged from 1.07 to 1.11. Cyclophosphamide (CTX) had a radioprotective effect (DEF 0.90), whereas 5-fluorouracil (5-FU) had no effect (DEF 1.00). The effect of ADM was present at administration from 6 h before to 2 min after irradiation, and the effect of BLM from 24 h before to 4 h after irradiation. The radioprotective effect of CTX and the enhanced effect of MM-C were only present on administration 15 min before and 2 min after irradiation. MTX and cis-DDP enhanced the skin reactions only when given before irradiation.     

电离辐射损伤医学防护剂研究进展

当今电离辐射已成为威胁人类健康的重要因素,探索有效的防护策略是放射医学领域研究的重要课题。及时使用辐射防护剂是减少电离辐射对机体正常组织损害最直接有效的方法,大量基于清除自由基、增强DNA损伤修复、诱导辐照组织缺氧及旁效应阻滞等机制的新型辐射防护剂逐渐被开发。本文总结了近年来国内外研究报道的多种辐射防护剂及其潜在的分子生物学机制,为探索新型电离辐射医学防护制剂提供理论参考。     

Determination of energy absorption and exposure buildup factors by using G-P fitting approximation for radioprotective agents

Purpose: Recently, there has been an increase in interest into research into radioprotective agents. Radioprotectors are compounds that protect against radiation injury when given orally (through drinking water) prior to radiation exposure. The purpose is to achieve preferred protection of normal tissues against injury inflicted by ionizing radiation used to treat tumors. The main aim of this work is to investigate energy absorption (EABF) and exposure buildup factors (EBF) of commonly used some radioprotective agents.

Materials and methods: We have used the Geometric Progression (G-P) fitting method for calculating the equivalent atomic number (Z_eq), for EABF and EBF buildup factors of the radioprotective agents in the energy range 0.015–15?MeV for penetration depths up to 40 mean free path.

Results: Significant variations in both EABF and EBF values were observed for several agents at the moderate energy region. At energies below 0.1?MeV, EABF and EBF values increased with decreasing equivalent atomic number Z_eq of the samples. At energies >0.15?MeV, EABF and EBF values were found to decrease with decreasing Z_eq of all agents. In addition, EABF and EBF were the largest for carnosin, tempol, melatonin, interferon gamma and orientine at 0.05 and 0.06?MeV, respectively, and the minimum values of buildup factors were at 0.1?MeV for cysteine, amifostine, penicillamine and glutathione.

Conclusions: Cysteine and amifostine are good compounds for gamma rays absorption applications among the selected compounds. The presented results in this study are expected to be helpful in radiation dosimetry.     

Dependence of Radioprotective Effect of Chemical Modifying Agents on Their Intracellular Concentrations

Summary

Regularities of the radioprotective effect of chemical modifying agents cysteamine, caffeine benzoate, thioglycolic acid, and caffeine, all weak electrolytes, have been studied in cultured Chinese hamster cells. Efficiency of protection is shown to be dependent on pH and concentrations of the drug inside the cells and in the medium. Based on the theory of the dissociation of weak electrolytes and their distribution between the cells and the medium a strong correlation between the efficiency of modification of the radiation response and intracellular concentration of a modifying agent is shown.     

Study of the radioprotective effects of TMG on teratogenic malformations in irradiated mice

ICR mice fetuses in the organogenesis stage were used to clarify experimentally the mechanism of the protective effect of vitamin E derivant (TMG: 2-(alpha-D-Glucopyranosyl) methyl-2, -5, -7, -8-Teramethylchorman-6-working woman) on the effects of radiation. The authors paid careful attention to radiation, and the radioprotective effects of TMG on the induction of malformations was examined. Radiation is an important consideration because of its widespread use in the areas of medicine, nuclear energy, and industry. Malformations induced by radiation at the organogenesis stage, skeletal malformations, and the effects at the cellular level of embryos were examined in this research. Further, the mechanism of the protection effect of TMG against radiation-induced malformations was analyzed and observed experimentally. Thus, this study was done to provide fundamental data on the radioprotective agent TMG. It was clear that TMG exerted radioprotective effects against embryonic death and the rate of teratogenesis when administered before exposure. Such effects were also exerted against skeletal malformations and fetal body weight. In summary, radioprotective effects were observed at the whole-body level as well as at the cellular level.