Ward H E, Kemsley L, Davies L, Holecek M, Berend N
Department of Thoracic Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Radiat Res. 1993 Oct;136(1):22-8.
We have used a model of bilateral radiation-induced lung disease in the rat to study the effects of corticosteroids. This model is characterized by interstitial edema at 2 weeks after radiotherapy followed by florid alveolitis with an alveolar protein leak which peaks at 4 weeks. Mast cell density peaks at 7 weeks, and there is a progressive increase in lung collagen (fibrosis) from 5 to 20 weeks. Intraperitoneal corticosteroids or saline were given at the time of irradiation or sham irradiation (protocol 1), every second day during weeks 3 and 4 (protocol 2), or three times weekly during weeks 3 to 8 (protocol 3). In protocol 1, steroids protected the lung from interstitial edema at 2 weeks, delayed the alveolitis without reducing its intensity, and significantly reduced the alveolar protein leak. However, radiation fibrosis was not reduced at 20 weeks. Longer steroid administration (protocol 2) suppressed the alveolar protein leak and delayed and significantly reduced the severity of the inflammatory cell response. Although the tissue mast cell and fibrotic responses were suppressed during and for at least 3 weeks after steroids, the ultimate fibrotic reaction was the same in both irradiated groups. In protocol 3, steroids suppressed the alveolitis and delayed the rise in tissue mast cell density, but did not affect the fibrotic response at 20 weeks. These studies suggest that steroids can suppress the alveolitis provided they are used throughout the period of alveolitis. Although they also delay the tissue mast cell response to radiation, the ultimate fibrosis is not altered. This provides further evidence for the dissociation of alveolitis and fibrosis after lung irradiation and has potential implications for management of radiation-induced lung disease in humans.
我们使用大鼠双侧放射性肺病模型来研究皮质类固醇的作用。该模型的特点是放疗后2周出现间质性水肿，随后是肺泡炎伴肺泡蛋白渗漏，在4周时达到峰值。肥大细胞密度在7周时达到峰值，肺胶原蛋白（纤维化）从5周到20周逐渐增加。在照射或假照射时给予腹腔内皮质类固醇或生理盐水（方案1），在第3周和第4周每隔一天给予（方案2），或在第3周到第8周每周给予三次（方案3）。在方案1中，类固醇在2周时保护肺免受间质性水肿，延迟肺泡炎但不降低其强度，并显著减少肺泡蛋白渗漏。然而，在20周时放射性纤维化并未减轻。更长时间的类固醇给药（方案2）抑制了肺泡蛋白渗漏，延迟并显著降低了炎症细胞反应的严重程度。尽管在给予类固醇期间及之后至少3周组织肥大细胞和纤维化反应受到抑制，但两个照射组的最终纤维化反应相同。在方案3中，类固醇抑制了肺泡炎并延迟了组织肥大细胞密度的升高，但在20周时未影响纤维化反应。这些研究表明，只要在整个肺泡炎期间使用，类固醇就能抑制肺泡炎。尽管它们也延迟了组织肥大细胞对辐射的反应，但最终纤维化并未改变。这为肺照射后肺泡炎和纤维化的分离提供了进一步的证据，并对人类放射性肺病的管理具有潜在意义。
