Nebulisation of synthetic lamellar lipids mitigates radiation-induced lung injury in a large animal model.

Nebulisation of synthetic lamellar lipids mitigates radiation-induced lung injury in a large animal model.
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合成层状脂质的雾化可缓解大型动物模型中辐射诱导的肺损伤。

DOI:
10.1038/s41598-018-31559-3
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发表时间:
2018-09-06
期刊:
影响因子:
4.6
通讯作者:
Parys M
Parys M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Collie D;Murchison JT;Wright SH;McLean A;Howard L;Del-Pozo J;Smith S;McLachlan G;Lawrence J;Kay E;Schwarz T;Parys M

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防止辐射诱发肺损伤(RILI)的方法将有助于制定更有效的肺癌放射治疗方案,并可能提供在发生故意或意外核或放射事件时保护更广泛人群的手段。我们假设通过雾化合成的层状脂质来补充脂质膜可以减轻RILI。在用雾化层状脂质或生理盐水预处理后,麻醉的绵羊被规定分次放疗(30戈瑞(戈伊)总剂量,以3-4天的间隔分5次6戈伊)至限定的单侧肺体积。首次放射治疗后37天放射暴露肺的大体病理学在治疗组之间一致,包括胸膜表面明显的深红色充血和触诊时的硬度。放射性暴露肺中一致的组织病理学特征为胸膜下、动脉周围和支气管周围肺泡内水肿、肺泡纤维化、间质性肺炎和II型肺细胞增生。与盐水处理的绵羊相比,合成的层状脂质消除了辐射诱导的肺泡纤维化,并降低了辐射暴露肺中的α-平滑肌肌动蛋白(ASMA)表达。合成板层脂质的管理也与整个肺中表达树突状细胞-溶酶体相关膜蛋白的细胞数量增加有关。
Methods to protect against radiation-induced lung injury (RILI) will facilitate the development of more effective radio-therapeutic protocols for lung cancer and may provide the means to protect the wider population in the event of a deliberate or accidental nuclear or radiological event. We hypothesised that supplementing lipid membranes through nebulization of synthetic lamellar lipids would mitigate RILI. Following pre-treatment with either nebulised lamellar lipids or saline, anaesthetised sheep were prescribed fractionated radiotherapy (30 Gray (Gy) total dose in five 6 Gy fractions at 3–4 days intervals) to a defined unilateral lung volume. Gross pathology in radio-exposed lung 37 days after the first radiation treatment was consistent between treatment groups and consisted of deep red congestion evident on the pleural surface and firmness on palpation. Consistent histopathological features in radio-exposed lung were subpleural, periarteriolar and peribronchial intra-alveolar oedema, alveolar fibrosis, interstitial pneumonia and type II pneumocyte hyperplasia. The synthetic lamellar lipids abrogated radiation-induced alveolar fibrosis and reduced alpha-smooth muscle actin (ASMA) expression in radio-exposed lung compared to saline treated sheep. Administration of synthetic lamellar lipids was also associated with an increased number of cells expressing dendritic cell-lysosomal associated membrane protein throughout the lung.
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