Department of Nutritional Sciences,School of Biosciences and Medicine, Faculty of Health and Medical Sciences,University of Surrey,Guildford GU2 7XH,UK.
Nutr Res Rev. 2017 Jun;30(1):50-72. doi: 10.1017/S0954422416000238. Epub 2017 Jan 23.
The regulation of linear growth by nutritional and inflammatory influences is examined in terms of growth-plate endochondral ossification, in order to better understand stunted growth in children. Linear growth is controlled by complex genetic, physiological, and nutrient-sensitive endocrine/paracrine/autocrine mediated molecular signalling mechanisms, possibly including sleep adequacy through its influence on growth hormone secretion. Inflammation, which accompanies most infections and environmental enteric dysfunction, inhibits endochondral ossification through the action of mediators including proinflammatory cytokines, the activin A-follistatin system, glucocorticoids and fibroblast growth factor 21 (FGF21). In animal models linear growth is particularly sensitive to dietary protein as well as Zn intake, which act through insulin, insulin-like growth factor-1 (IGF-1) and its binding proteins, triiodothyronine, amino acids and Zn2+ to stimulate growth-plate protein and proteoglycan synthesis and cell cycle progression, actions which are blocked by corticosteroids and inflammatory cytokines. Observational human studies indicate stunting to be associated with nutritionally poor, mainly plant-based diets. Intervention studies provide some support for deficiencies of energy, protein, Zn and iodine and for multiple micronutrient deficiencies, at least during pregnancy. Of the animal-source foods, only milk has been specifically and repeatedly shown to exert an important influence on linear growth in both undernourished and well-nourished children. However, inflammation, caused by infections, environmental enteric dysfunction, which may be widespread in the absence of clean water, adequate sanitation and hygiene (WASH), and endogenous inflammation associated with excess adiposity, in each case contributes to stunting, and may explain why nutritional interventions are often unsuccessful. Current interventions to reduce stunting are targeting WASH as well as nutrition.
为了更好地理解儿童生长迟缓，本文从生长板骺软骨内骨化的角度研究了营养和炎症对线性生长的调节作用。线性生长受复杂的遗传、生理和营养敏感的内分泌/旁分泌/自分泌介导的分子信号机制控制，可能包括通过其对生长激素分泌的影响来保证充足的睡眠。炎症伴随着大多数感染和环境肠道功能障碍，通过包括促炎细胞因子、激活素 A-卵泡抑素系统、糖皮质激素和成纤维细胞生长因子 21 (FGF21) 在内的介质抑制骺软骨内骨化。在动物模型中，线性生长对膳食蛋白质和锌摄入特别敏感，它们通过胰岛素、胰岛素样生长因子-1 (IGF-1) 及其结合蛋白、三碘甲状腺原氨酸、氨基酸和 Zn2+ 作用，刺激生长板蛋白和蛋白聚糖合成以及细胞周期进程，这些作用被皮质类固醇和炎症细胞因子阻断。观察性人类研究表明，生长迟缓与营养差、主要是植物性饮食有关。干预研究为能量、蛋白质、锌和碘缺乏以及多种微量营养素缺乏提供了一些支持，至少在怀孕期间是这样。在动物源性食物中，只有牛奶被明确且反复证明对营养不足和营养良好的儿童的线性生长有重要影响。然而，由感染、环境肠道功能障碍引起的炎症（在缺乏清洁水、充足的卫生和卫生设施 (WASH) 的情况下可能广泛存在）以及与肥胖过多相关的内源性炎症，都会导致生长迟缓，这可能解释了为什么营养干预往往不成功。目前减少生长迟缓的干预措施是针对 WASH 和营养。
