BACKGROUND & AIMS:
OBJECTIVE:Early nutritional environment may program permanent metabolic alterations, predisposing to later diseases. We have investigated the interference of maternal malnutrition during lactation with the development of acute inflammation in adult rats.
MATERIALS AND METHODS:Adult rats, offspring of dams fed with either protein-free diet (UN group) or 22% protein diet (C group) during the first 10 days of lactation, were submitted to pleurisy with carrageenan (500 microg/cavity). Pleural edema, neutrophil migration and ICAM expression, were evaluated 4 h after and correlated with alterations in plasma insulin and corticosterone. Leukocyte-endothelium interactions were evaluated by intravital microscopy 1 h after inflammation.
RESULTS:Compared to controls, UN rats showed a decrease in pleural edema formation (50%), neutrophil migration (50%), endothelial ICAM-1 expression on pulmonary tissue, and impairment in leukocyte adhesion (50%) and migration (80%) through endothelium. Circulating insulin was lower (42%) and corticosterone was higher (34%) in UN, compared to controls. Pre-treatment of UN with insulin (5 IU/day) or RU486 (20 mg/kg/day), inhibitor of glucocorticoid receptor, restored leukocyte functions and ICAM-1 expression.
CONCLUSION:Postnatal maternal malnutrition, programming for permanent alterations in insulin and glucocorticoid secretion in progeny, that were unable to properly mount an inflammatory response, probably predisposes to chronic diseases in adult life.
背景与目标:
目的:早期的营养环境可能会导致永久性的代谢改变,从而导致以后的疾病。我们已经研究了哺乳期母体营养不良与成年大鼠急性发炎的关系。
材料与方法:成年大鼠,哺乳期前10天以无蛋白饮食(UN组)或22%蛋白饮食(C组)喂养的水坝后代,被角叉菜胶(每腔500微克)进行胸膜炎。 4小时后评估胸膜水肿,中性粒细胞迁移和ICAM表达,并与血浆胰岛素和皮质酮的变化相关。炎症1小时后,通过活体显微镜评估白细胞-内皮的相互作用。
结果:与对照组相比,UN大鼠的胸膜水肿形成减少(50%),中性粒细胞迁移减少(50%),肺组织内皮ICAM-1表达减少,白细胞粘附减少(50%)和迁移减少(80%) )通过内皮细胞。与对照组相比,联合国的循环胰岛素较低(42%),皮质酮较高(34%)。用胰岛素(5 IU /天)或RU486(20 mg / kg /天),糖皮质激素受体抑制剂,UN预处理,恢复白细胞功能和ICAM-1表达。
结论:产后母亲营养不良,为子代中的胰岛素和糖皮质激素分泌的永久性改变制定程序,这些改变无法适当地引起炎症反应,这可能是成人生活中慢性病的诱因。