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灵长类动物模型中臭氧增强铂诱导的哮喘

Ozone enhancement of platinum asthma in a primate model.

作者信息

Biagini R E, Moorman W J, Lewis T R, Bernstein I L

出版信息

Am Rev Respir Dis. 1986 Oct;134(4):719-25. doi: 10.1164/arrd.1986.134.4.719.

DOI:10.1164/arrd.1986.134.4.719
PMID:3767128
Abstract

Three groups of adult male cynomolgus monkeys (Macaca fascicularis) were exposed to either 200 micrograms/m3 ammonium hexachloroplatinate [(NH4)2PtCl6], 200 micrograms (NH4)2PtCl6 concurrently with 1 ppm ozone (O3), or to 1 ppm O3 only. The animals were exposed by inhalation for 6 h per day, 5 days per week for 12 wk. The experimental design included methacholine preexposure and Na2PtCl6 bronchoprovocation challenge evaluations, Na2PtCl6 threshold skin tests, and sera for analyses of antibodies. Two weeks after the 12-wk exposures, these same indices were reevaluated. Baseline pulmonary function was not significantly affected by the exposure regimens; however, the combination of exposure to O3 and (NH4)2PtCl6 significantly reduced the concentration of platinum (Pt) salt and methacholine necessary to increase average pulmonary flow resistance (RL) 200% (EC200 RL). Ozone or Pt exposure alone had no significant effect on these parameters. Platinum and methacholine EC200 RL values were highly correlated for both Pt-exposed groups after exposure. These data indicated that combined O3 and Pt exposure significantly increased specific (Pt) and nonspecific (methacholine) bronchial hyperreactivity more often than did exposure to either O3 or the Pt salt alone. Combined O3 plus Pt exposure also significantly increases the incidence of positive Pt skin tests when compared with the other exposure groups. Similar to the human experience, radioallergosorbent testing (RAST) for Pt-specific antibodies was not as sensitive as direct skin testing in identifying allergic persons.

摘要

将三组成年雄性食蟹猴(猕猴)分别暴露于浓度为200微克/立方米的六氯铂酸铵[(NH4)2PtCl6]、200微克(NH4)2PtCl6与1 ppm臭氧(O3)的混合物,或仅暴露于1 ppm O3中。动物每天经吸入暴露6小时,每周5天,共12周。实验设计包括乙酰甲胆碱预暴露和六氯铂酸钠支气管激发试验评估、六氯铂酸钠阈值皮肤试验以及用于抗体分析的血清检测。在12周暴露结束两周后,对这些相同指标进行重新评估。基线肺功能未受到暴露方案的显著影响;然而,暴露于O3和(NH4)2PtCl6的组合显著降低了使平均肺血流阻力(RL)增加200%(EC200 RL)所需的铂(Pt)盐和乙酰甲胆碱的浓度。单独暴露于臭氧或铂对这些参数没有显著影响。暴露后,两个铂暴露组的铂和乙酰甲胆碱EC200 RL值高度相关。这些数据表明,与单独暴露于O3或铂盐相比,O3和铂联合暴露更常显著增加特异性(铂)和非特异性(乙酰甲胆碱)支气管高反应性。与其他暴露组相比,O3加铂联合暴露还显著增加了铂皮肤试验阳性的发生率。与人类情况相似,用于检测铂特异性抗体的放射变应原吸附试验(RAST)在识别过敏个体方面不如直接皮肤试验敏感。

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