Fujino Y, Okada T, Takeda K, Kobayashi Y, Yoshiya I
Nihon Kyobu Shikkan Gakkai Zasshi. 1989 Feb;27(2):180-7.
To elucidate the pathogenesis of adult respiratory distress syndrome (ARDS), bleomycin is often used to induce lung injury because of is acute inflammatory and late fibrogenic effects on the lung. This study was undertaken to determine if fibroblast growth factors or suppressive factors might exist in bronchoalveolar lavage fluid (BALF) when acute lung injury is induced by bleomycin in rats. In the experimental group, 1.5 U of bleomycin was administered intratracheally, whereas in the control group, saline solution was given. In both groups, rats were sacrificed serially up to 4 wks. In each rat, bronchoalveolar lavage was done three times using an aliquot of 5 ml saline solution. BALF was centrifuged to obtain cells and supernatants which were further fractionated by gel-filtration. Fibroblast stimulatory and inhibitory activities were evaluated by [3H]-thymidine incorporation by fibroblasts. In the experimental group, the recovered cell count increased threefold compared with the control group and most of the increase was attributed to the increase of neutrophil. The fraction whose molecular weight is about 20,000 potentiated the [3H]-thymidine incorporation by fibroblast and its peak activity was found on the 5th day after BLM administration. On the other hand, the fraction of small molecular weight (less than 1,000) showed inhibitory activity which did not change throughout the study period. These results suggest that the imbalance between the fibroblast stimulatory and inhibitory activities after the acute lung injury may have a key role to develop pulmonary fibrosis.
为阐明成人呼吸窘迫综合征(ARDS)的发病机制,博来霉素常被用于诱导肺损伤,因为它对肺具有急性炎症和晚期纤维化作用。本研究旨在确定当博来霉素诱导大鼠急性肺损伤时,支气管肺泡灌洗液(BALF)中是否可能存在成纤维细胞生长因子或抑制因子。实验组经气管内给予1.5 U博来霉素,而对照组给予盐溶液。在两组中,大鼠被连续处死直至4周。在每只大鼠中,用5 ml盐溶液等分试样进行三次支气管肺泡灌洗。将BALF离心以获得细胞和上清液,然后通过凝胶过滤进一步分级分离。通过成纤维细胞掺入[3H] - 胸苷来评估成纤维细胞刺激和抑制活性。在实验组中,回收的细胞计数比对照组增加了三倍,且大部分增加归因于中性粒细胞的增加。分子量约为20,000的级分增强了成纤维细胞对[3H] - 胸苷的掺入,其峰值活性在给予博来霉素后第5天出现。另一方面,小分子量级分(小于1000)显示出抑制活性,且在整个研究期间没有变化。这些结果表明,急性肺损伤后成纤维细胞刺激和抑制活性之间的失衡可能在肺纤维化的发展中起关键作用。