Sakuma Tsutomu, Zhao Yabin, Sugita Makoto, Sagawa Motoyasu, Toga Hirohisa, Ishibashi Takaharu, Nishio Matomo, Matthay Michael A
Department of Thoracic Surgery, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
Am J Physiol Lung Cell Mol Physiol. 2004 Jun;286(6):L1268-74. doi: 10.1152/ajplung.00229.2003. Epub 2004 Feb 20.
Inadequate nutrition complicates the clinical course of critically ill patients, and many of these patients develop pulmonary edema. However, little is known about the effect of malnutrition on the mechanisms that resolve alveolar edema. Therefore, we studied the mechanisms responsible for the decrease in alveolar fluid clearance in rats exposed to malnutrition. Rats were allowed access to water, but not to food, for 120 h. Then, the left and right lungs were isolated for the measurement of lung water volume and alveolar fluid clearance, respectively. The rate of alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue dye that was instilled into the distal air spaces with an isosmolar 5% albumin solution over 1 h. Malnutrition decreased alveolar fluid clearance by 38% compared with controls. Amiloride (10(-3) M) abolished alveolar fluid clearance in malnourished rats. Either refeeding for 120 h following nutritional deprivation for 120 h or an oral supply of sodium glutamate during nutritional deprivation for 120 h restored alveolar fluid clearance to 91 and 86% of normal, respectively. Dibutyryl-cGMP, a cyclic nucleotide-gated cation channel agonist, increased alveolar fluid clearance in malnourished rats supplied with sodium glutamate. Terbutaline, a beta(2)-adrenergic agonist, increased alveolar fluid clearance in rats under all conditions (control, malnutrition, refeeding, and glutamate-treated). These results indicate that malnutrition impairs primarily amiloride-insensitive and dibutyryl-cGMP-sensitive alveolar fluid clearance, but this effect is partially reversible by refeeding, treatment with sodium glutamate, or beta-adrenergic agonist therapy.
营养不足会使重症患者的临床病程复杂化，并且这些患者中有许多会出现肺水肿。然而，关于营养不良对肺泡水肿消退机制的影响却知之甚少。因此，我们研究了营养不良大鼠肺泡液体清除率降低的相关机制。将大鼠禁食120小时，但可饮水。然后，分别分离左肺和右肺以测量肺水含量和肺泡液体清除率。通过在1小时内将伊文思蓝染料与等渗5%白蛋白溶液注入远端气腔，随着染料浓度的逐渐增加来测量肺泡液体清除率。与对照组相比，营养不良使肺泡液体清除率降低了38%。氨氯吡咪（10⁻³ M）消除了营养不良大鼠的肺泡液体清除率。在禁食120小时后再喂食120小时，或在禁食120小时期间口服谷氨酸钠，可分别使肺泡液体清除率恢复至正常水平的91%和86%。二丁酰环磷鸟苷，一种环核苷酸门控阳离子通道激动剂，可增加补充谷氨酸钠的营养不良大鼠的肺泡液体清除率。特布他林，一种β₂肾上腺素能激动剂，在所有条件下（对照、营养不良、再喂食和谷氨酸处理）均可增加大鼠的肺泡液体清除率。这些结果表明，营养不良主要损害对氨氯吡咪不敏感且对二丁酰环磷鸟苷敏感的肺泡液体清除率，但这种影响可通过再喂食、谷氨酸钠治疗或β肾上腺素能激动剂治疗部分逆转。
