地方性燃煤型砷中毒的生物化学研究

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	地方性燃煤型砷中毒的生物化学研究
其他题名	Study on biochemistry of endemic arsenicosis derived from combustion of high-arsenic coal
	邓国栋
学位类型	博士
	2008-05-26
学位授予单位	中国科学院地球化学研究所
学位授予地点	地球化学研究所
学位名称	博士
关键词	煤砷中毒砷负荷卟啉生物标志生物化学
摘要	目的　研究燃煤型砷中毒疾病发生发展的生物化学机制和卟啉作为早期燃煤型砷暴露生物标志的可能性。方法　主要进行两方面的研究，一是根据内蒙古前期研究中建立的方法，采用砷负荷评估方法－二巯基丁二酸(DMSA)试验，测定贵州燃煤型砷中毒区患者和对照体内砷负荷（形态和数量），通过病例对照研究，了解燃煤型砷中毒患者体内砷负荷的特点、砷代谢的机制，同时通过对比内蒙古饮水型砷中毒区的研究数据，了解二型砷中毒患者体内砷负荷的差别及成因。二是通过暴露对照、不同年龄和性别分层对比系统研究燃煤型砷暴露对卟啉排泄的影响。结果 1. 在国内外首次建立了采用DMSA(二巯基丁二酸)试验评估砷中毒人群砷负荷的方法，并在燃煤型砷中毒区予以实施。 2. 利用DMSA能够络合移除体内的砷，特别是MMA，显示具有用于评估体内砷负荷和健康风险的潜在可能性； 3. 工作中发现一些砷中毒区病人在停用高砷煤很长时间后（>30y）体内砷负荷仍然很高； 4. 研究表明DMSA能够促进MMA3+排出，移除体内贮存的砷，从而降低砷对人体的远期致癌风险。 5. 首次在尿中检测出与DMSA结合的两种砷复合物，这一发现此前还未有过报道，该发现对进一步了解巯基类药物的排砷机制提供了重要信息，具有重要的意义； 6. 在砷暴露对卟啉影响研究方面，发现低龄组（<20y）尿卟啉Ⅲ和粪卟啉Ⅲ比对照显著增高，此外，砷暴露组尿液中砷与总粪卟啉和总卟啉呈正相关，这说明卟啉具有作为早期燃煤型砷暴露生物标志潜在价值。
其他摘要	Objective To study the biochemical mechanisms for arsenicosis development and possibility of porphyrins as biomarkers for early arsenic exposure derived from combustion of high-arsenic coal. Methods The research contained two items, one was to determine the arsenic burden (arsenic species and amount) of control group and arsenicosis group derived from combustion of high-arsenic coal in Guizhou by DMSA test based on the way from the prophase research for arsenicosis patients for drinking high-arsenic water in Inner Mongolia, and then study the characteristics of arsenic burden of arsnicosis patients through comparing it between case and control, and mechanism of arsenic biotransformation in vivo; in additional, through comparing arsenic burden between two types of arsenicosis, it was also studied for the difference and causes. The other one was to study the effects of early arsenic exposure derived from combustion of high-arsenic coal on the porphyrins excretion through comparing it between exposure and control, different ages and both sexes. Conclusion 1. It was first time to use the way DMSA (2,3-Dimercaptosuccinic acid) test for arsenic burden assessment of arsenicosis patients derived from combustion of high-arsenic coal in Guizhou. 2. Some of arsenic in body was removed by DMSA, especially for MMA, and this showed the possibility of use of DMSA for assessment of arsenic burden and health risk. 3. Some of the arsenicosis patients were found to have higher arsenic burden than control in this study, despite stopping use of the high-arsenic coal more than 30 years. 4. It was shown that administration of DMSA could accelerate the MMA3+ excretion reducing the cancer risk of long term. 5. It was first time to identify two arsenic compounds bound with DMSA，which was never reported before. This finding was significant, and would provide useful information in study on mechanism of double-thiol drugs in removing arsenic in vivo. 6. Concerning the study of effects of arsenic exposure on porphyrins, it was found that concentrations of uroporphyrin-Ⅲ and coporporphyrin-Ⅲ for young group (<20y) were higher than control’s, and there were positive correlations between urinary arsenic and total coporporphyrin, and total porphyrin, which suggested that porphyrins were possible to be used as biomarkers for early exposure derived from combustion of high-arsenic coal.
页数	96
语种	中文
文献类型	学位论文
条目标识符	http://ir.gyig.ac.cn/handle/352002/3164
专题	研究生_研究生_学位论文
推荐引用方式 GB/T 7714	邓国栋. 地方性燃煤型砷中毒的生物化学研究[D]. 地球化学研究所. 中国科学院地球化学研究所,2008.

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