Doelman C J, Leurs R, Oosterom W C, Bast A
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Exp Lung Res. 1990 Jan;16(1):41-55. doi: 10.3109/01902149009064698.
Chronic exposure to several types of mineral dust particles induces an inflammatory reaction in the lung. Dust particles activate alveolar macrophages and prime leukocytes (neutrophils, eosinophils, and basophils), leading to an enhanced release of reactive oxygen species. Sometimes mineral dust particles also contain radicals. Reactive oxygen species (superoxide anion radical, hydrogen peroxide, hydroxyl radical, and singlet oxygen) may lead to tissue damage. These are able to break DNA strands, to destroy proteins, and to induce the process of lipid peroxidation. The effects of oxygen radicals on the beta-adrenergic and muscarinic receptor response of the guinea pig and rat tracheal strip are described. The beta-adrenergic receptor response appeared to be more susceptible to oxidative stress than the muscarinic receptor response. This may lead to an autonomic imbalance on exposure to oxygen radicals. The lipid peroxidation product 4-hydroxy-2,3-trans-nonenal diminished the beta-adrenergic responsiveness in guinea pig tracheal preparations. Histologic examinations indicated that at low concentrations of cumene hydroperoxide (10(-4) M) the epithelial layer of rat trachea was already destroyed, whereas no effect on the muscarinic response was found. Oxygen radical-mediated damage in lung tissue may lead to lung emphysema, hyperresponsiveness, and hypersensitivity. Pharmacotherapeutic interventions that prevent initiation or propagation of these free radical reactions may have a beneficial effect in mineral dust-associated lung disease.
长期暴露于几种类型的矿物粉尘颗粒会在肺部引发炎症反应。粉尘颗粒激活肺泡巨噬细胞并使白细胞（中性粒细胞、嗜酸性粒细胞和嗜碱性粒细胞）致敏，导致活性氧物质的释放增加。有时矿物粉尘颗粒还含有自由基。活性氧物质（超氧阴离子自由基、过氧化氢、羟基自由基和单线态氧）可能导致组织损伤。这些物质能够断裂DNA链、破坏蛋白质并诱导脂质过氧化过程。本文描述了氧自由基对豚鼠和大鼠气管条β-肾上腺素能受体和毒蕈碱受体反应的影响。β-肾上腺素能受体反应似乎比毒蕈碱受体反应更容易受到氧化应激的影响。这可能导致暴露于氧自由基时出现自主神经失衡。脂质过氧化产物4-羟基-2,3-反式壬烯醛降低了豚鼠气管制剂中的β-肾上腺素能反应性。组织学检查表明，在低浓度的氢过氧化异丙苯（10⁻⁴ M）下，大鼠气管的上皮层已经被破坏，而对毒蕈碱反应没有影响。肺组织中氧自由基介导的损伤可能导致肺气肿、高反应性和超敏反应。预防这些自由基反应启动或传播的药物治疗干预可能对矿物粉尘相关的肺部疾病有有益作用。
