STUDIES ON THE EFFECTS OF DIESEL EXHAUST PARTICLES ON HUMAN HEALTH

柴油机尾气颗粒对人体健康影响的研究

• 批准号: 07680588
• 负责人: MORI Yoki
• 金额: $ 1.6万
• 依托单位: HEALTH SCIENCES UNIVERSITY OF HOKKAIDO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07680588/
• 关键词: diesel exhaust particles; reactive oxygen intermediates; catalase; alternative pathway of complement; 活性酸素生成物質; 補体活性化

Diesel cars exhaust 30-100 times more particles (DEP) than do gasoline engine cars. DEP is one of the most important air pollution substances, especially, in the big city. Previously, the authors found that DEP could react with oxygen to produce superoxide anion radicals (O_2^-・) in vitro without any biological activating systems. In order to know, furthermore, the mechanism of biological effects of DEP on human health related to reactive oxygen intermediates, we aimed to 1) isolate and identify the compounds responsible for generation of O_2^-・in DEP,and 2) estimate the inhibitory activity of DEP components on catalase activity which is the scavenger of reactive oxygen intermediate. And furthermore, the effects of DEP on the complement activity was evaluated.1) DEP were extracted serially, with hexane, benzene, dichloromethane, and methanol, and it was found that O_2^-・generation substances were distributed to each 4 extracts indicating that heterogeneous compounds in DEP could generate O_2^-・Superoxide anion producing activity of these extracts were increased seriously by reduction with NADPH and P450 reductase. With column chromatography and HPLC,a O_2^-・producing substance was isolated and the chemical structure was identified as 1-methyl-3-hydroxyphthalate. 2) Buffer extract of DEP could inhibit the activity of catalase, in the presence of chloride ion. Thus, DEP could injury human health by producing reactive oxygen intermediates (ROI), and inhibition of degradation of ROI.Furthermore, DEP extract could activate the alternative pathway of human complement system.From these studies, it was found that DEP inhaled and deposed in trachea could injury cells and induce pulmonary disease with some different mechanisms.

柴油汽车排放的颗粒物（DEP）比汽油发动机汽车多30-100倍。DEP是大气污染的主要物质之一，特别是在大城市。在此之前，作者发现DEP在体外不需要任何生物活化系统就能与氧反应产生超氧阴离子自由基（O_2^-·）。此外，为了进一步了解与活性氧中间体相关的DEP对人类健康的生物学效应机制，我们的目标是：1）分离和鉴定DEP中负责产生O_2^-·的化合物，2）评估DEP组分对过氧化氢酶活性的抑制活性。过氧化氢酶是活性氧中间体的清除剂。1）用正己烷、苯、二氯甲烷、甲醇连续提取DEP，O_2^-·产生物质分布在4种提取物中，表明DEP中的非均相化合物能产生O_2^-·经NADPH和P450还原酶还原后，超氧阴离子产生活性显著提高。通过柱层析和高效液相色谱分离得到一种产O_2^-·物质，经鉴定其化学结构为1-甲基-3-羟基邻苯二甲酸酯。2)在氯离子存在下，DEP的缓冲提取物对过氧化氢酶有抑制作用。因此，DEP可通过产生活性氧中间产物（ROI），抑制ROI降解，激活补体系统旁路途径，从而对人体健康造成危害，研究发现吸入并经气管沉积的DEP可通过不同的机制损伤细胞，诱发肺部疾病。

项目成果

Mori Y., Murakami S., Sagae T., Hayashi H., Sakata M., Kumagai Y., and Sagai M.: "Inhibition of Catalase Activity in vitro by Diesel Exhaust Particles" J.Toxicol.Environment.Health. 47. 125-134 (1996)

Mori Y.、Murakami S.、Sagae T.、Hayashi H.、Sakata M.、Kumagai Y. 和 Sagai M.：“柴油机尾气颗粒对体外过氧化氢酶活性的抑制”J.Toxicol.Environment.Health。

Y.Mori,S.Murakami,H.Hayashi,M.Sagai: "Inhibition of catalase activity in vitro by diesel exhaust particles" Jounal of Toxicology and Environmental Health. 47(2). 125-134 (1996)

Y.Mori、S.Murakami、H.Hayashi、M.Sagai：“柴油机尾气颗粒对体外过氧化氢酶活性的抑制”毒理学与环境健康杂志。