重度肥胖引发心肺功能衰竭，补充亚精胺或可打破无特效治疗的魔咒

【文献解读】

来自德国汉诺威医学院功能与应用解剖学研究所的Julia Schipke教授研究团队发现肥胖会导致肺体积增大、肺泡数量增加、毛细血管内皮增厚、内皮表面积减少。补充亚精胺有效地缓解了肥胖相关的肺部结构的改变从而潜在地保护了肺部呼吸功能。

研究人员通过高脂饮食诱导C57BL/6N小鼠肥胖，期间补充或不补充亚精胺，30周后对肺部结构进行评估。结果发现，高脂饮食诱导了小鼠体重显著增加，肺体积也明显增加。补充亚精胺对体重增加没有影响，但显著降低了肺体积，接近正常饮食小鼠的肺体积。在小鼠肺实质中，高脂饮食使得肺腺泡空气和隔膜的体积以及肺泡表面积更大，肺泡数量比正常小鼠增加了一倍。补充亚精胺可减少肺腺泡中的空气量以及肺泡数量。此外，与正常小鼠相比，高脂饮食喂养小鼠的空气-血液屏障显著增厚，这主要是由于内皮细胞厚度增加。补充亚精胺可显著降低内皮细胞和空气-血液屏障的厚度。并且亚精胺治疗组小鼠上皮和内皮表面积更高，与正常组小鼠相似。

作者指出肥胖可造成肺泡气体交换区的结构重塑，这可能导致肥胖患者的肺功能损害和更高的呼吸系统疾病风险。补充亚精胺减轻了与肥胖相关的血管内皮改变，表明补充亚精胺对肥胖人群的肺功能有有益的影响。

【文献节选】

Obesity is associated with lung function impairment and respiratory diseases; however, the underlying pathophysiological mechanisms are still elusive, and therapeutic options are limited. This study examined the effects of prolonged excess fat intake on lung mechanics and microstructure and tested spermidine supplementation and physical activity as intervention strategies. C57BL/6N mice fed control diet (10% fat) or high-fat diet (HFD; 60% fat) were left untreated or were supplemented with 3 mM spermidine, had access to running wheels for voluntary activity, or a combination of both. After 30 wk, lung mechanics was assessed, and left lungs were analyzed by design-based stereology. HFD exerted minor effects on lung mechanics and resulted in higher body weight and elevated lung, air, and septal volumes. The number of alveoli was higher in HFD-fed animals. This was accompanied by an increase in epithelial, but not endothelial, surface area. Moreover, air-blood barrier and endothelium were significantly thicker. Neither treatment affected HFD-related body weights. Spermidine lowered lung volumes as well as endothelial and air-blood barrier thicknesses toward control levels and substantially increased the endothelial surface area under HFD. Activity resulted in decreased volumes of lung, septa, and septal compartments but did not affect vascular changes in HFD-fed mice. The combination treatment showed no additive effect. In conclusion, excess fat consumption induced alveolar capillary remodeling indicative of impaired perfusion and gas diffusion. Spermidine alleviated obesity-related endothelial alterations, indicating a beneficial effect, whereas physical activity reduced lung volumes apparently by other, possibly systemic effects.

【原文标题】Spermidine supplementation and voluntary activity differentially affect obesity-related structural changes in the mouse lung

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