Kennedy J I, Chandler D B, Fulmer J D, Wert M B, Grizzle W E
Department of Medicine, University of Alabama, Birmingham 35294.
Exp Lung Res. 1989 Mar;15(2):315-29. doi: 10.3109/01902148909087861.
Intratracheal bleomycin induces pulmonary fibrosis in experimental animals, but the mechanisms involved are poorly understood. Since altered levels of fatty acid metabolites are associated with bleomycin-induced lung injury, we examined the effects of a change in dietary fat on bleomycin-induced fibrosis. Previously we have shown that an essential fatty acid-deficient diet can reduce the severity of bleomycin-induced pulmonary fibrosis. The present study examined the effect of replacement of usual dietary fat with menhaden oil, rich in eicosapentaenoic acid, on the development of pulmonary fibrosis. Weanling rats were raised on a standard laboratory diet or a diet consisting of a fat-free powder to which was added 25% (w/w) of menhaden oil. After 8 weeks of feeding, the animals received either 1.5 units of bleomycin or an equivalent volume of saline intratracheally. In animals receiving the laboratory diet, bleomycin treatment produced a 44% increase in total lung protein content when compared to saline-treated controls (p less than 0.001) and a 77% increase in total lung hydroxyproline content (p less than 0.01). In contrast, bleomycin-treated animals receiving the menhaden oil diet had only small increases, which did not reach statistical significance, in protein and hydroxyproline content in the lung. Bronchoalveolar lavage cellularity did not differ among the treatment groups, but the percentage of lavage macrophages was slightly diminished in bleomycin-treated animals receiving the laboratory diet. Cellular differentials of lavage fluid did not differ significantly between bleomycin- and saline-treated animals receiving the menhaden oil diet. Bleomycin-induced histologic changes, quantitated by morphometric analysis, were significantly reduced with the menhaden oil diet. We conclude that a diet rich in eicosapentaenoic acid can significantly ameliorate bleomycin-induced pulmonary fibrosis, possibly via alterations in eicosanoid metabolism.
气管内注射博来霉素可在实验动物中诱发肺纤维化，但其中涉及的机制尚不清楚。由于脂肪酸代谢产物水平的改变与博来霉素诱导的肺损伤有关，我们研究了饮食脂肪变化对博来霉素诱导的纤维化的影响。此前我们已经表明，缺乏必需脂肪酸的饮食可以减轻博来霉素诱导的肺纤维化的严重程度。本研究检测了用富含二十碳五烯酸的鲱鱼油替代常规饮食脂肪对肺纤维化发展的影响。将断奶大鼠饲养在标准实验室饮食或由无脂粉末组成的饮食中，向其中添加25%（w/w）的鲱鱼油。喂养8周后，动物经气管内给予1.5单位博来霉素或等量的生理盐水。在接受实验室饮食的动物中，与生理盐水处理的对照组相比，博来霉素处理使肺总蛋白含量增加了44%（p<0.001），肺总羟脯氨酸含量增加了77%（p<0.01）。相比之下，接受鲱鱼油饮食的博来霉素处理动物的肺蛋白和羟脯氨酸含量仅略有增加，未达到统计学意义。支气管肺泡灌洗细胞数在各治疗组之间没有差异，但接受实验室饮食的博来霉素处理动物的灌洗巨噬细胞百分比略有下降。接受鲱鱼油饮食的博来霉素处理和生理盐水处理动物的灌洗液体细胞分类没有显著差异。通过形态计量分析定量的博来霉素诱导的组织学变化在鲱鱼油饮食组中显著减少。我们得出结论，富含二十碳五烯酸的饮食可以显著改善博来霉素诱导的肺纤维化，可能是通过改变类花生酸代谢实现的。
