Qiu Hai-Bo, Sun Hui-ming, Yang Yi, Zhuang Yu-gang, Chen Yan, Chen Yong-ming
Department of Critical Care Medicine, Hospital and School of Clinical Medicine, Southeast University, Nanjing 210009, China.
Zhonghua Yi Xue Za Zhi. 2006 Jan 17;86(3):187-91.
To determine the effect of dobutamine, a beta-adrenergic agonist, on the alveolar fluid clearance (AFC) in acute lung injury (ALI).
Thirty two male Sprague-Dawley rats were randomly divided into four equal groups: normal control group; ALI group, infused with endotoxin to induce ALI; dobutamine control group, receiving sustained intravenous injection of dobutamine at the dose of 5 microg/kg/min, and dobutamine treatment group, receiving sustained intravenous injection of dobutamine at the dose of 5 microg/kg/min after the administration of endotoxin. Experiment began 45-60 minutes after the circulation was stable. Blood pressure was measured and blood gas analysis was conducted at the beginning of the experiment and one hour later. Perfusion fluid with (125)I-albumin with the radioactivity of 1.5 microCi/ml was perfused into the lung. One hour after the mechanical ventilation the mice were killed and their lungs were taken out. Alveolar fluid was taken out to calculate the AFC by single nuclide tracer technique. RT-PCR was used to detect the expression of alpha, beta, and gamma-rat epithelial sodium channel (rENaC) mRNA.
(1) The AFC of ALI group was 14.0 +/- 1.2%, significantly lower than that of the normal control group (21.0 +/- 3.9%, P < 0.05). (2) The AFC of the dobutamine control group was 26.6 +/- 1.6%, significantly higher than that of the normal control group (P < 0.05). and the AFC of the dobutamine treatment group was 20.0 +/- 3.9%, significantly higher than that of the ALI group (P < 0.05). (3) The expression of a-rENaC mRNA was 1.40 +/- 0.40 in the ALI group and was 1.38 +/- 0.13 in the dobutamine treatment group, both significantly higher than those in the dobutamine control group (1.01 +/- 0.14) and in the normal control group (0.44 +/- 0.11, all P < 0.05). The expression of beta-rENaC mRNA was 0.70 +/- 0.8 in the ALI group was 0.71 +/- 0.17 in the dobutamine treatment group, both significantly higher than those in the dobutamine control group (0.58 +/- 0.12) and in the normal control group (0.44 +/- 0.11, all P < 0.05). There were not significant differences in expression of alpha and beta-rENaC mRNA between the normal control group and dobutamine control group, and between the ALI group and dobutamine treatment group (both P > 0.05). (4) The gamma-rENaC mRNA expression was 0.90 +/- 0.19 in the dobutamine control group and was 0.97 +/- 0.15 in the dobutamine treatment group, both significantly higher than that in the normal control group (0.69 +/- 0.10) and in the ALI group (0.70 +/- 0.32) (all P < 0.05).
Able to upregulate the gamma-rENaC expression and improve the AFC in acute lung injury, beta-adrenergic agonist may be beneficial to reduce lung edema in ALI patients.
确定β-肾上腺素能激动剂多巴酚丁胺对急性肺损伤（ALI）中肺泡液体清除率（AFC）的影响。
32只雄性Sprague-Dawley大鼠随机分为四组，每组数量相等：正常对照组；ALI组，注入内毒素诱导ALI；多巴酚丁胺对照组，以5μg/kg/min的剂量持续静脉注射多巴酚丁胺；多巴酚丁胺治疗组，在内毒素给药后以5μg/kg/min的剂量持续静脉注射多巴酚丁胺。在循环稳定后45 - 60分钟开始实验。在实验开始时及1小时后测量血压并进行血气分析。将放射性为1.5μCi/ml的（125）I-白蛋白灌注液灌注到肺中。机械通气1小时后处死小鼠并取出肺脏。取出肺泡液体，采用单标记核素示踪技术计算AFC。采用逆转录-聚合酶链反应（RT-PCR）检测α、β和γ-大鼠上皮钠通道（rENaC）mRNA的表达。
（1）ALI组的AFC为14.0±1.2%，显著低于正常对照组（21.0±3.9%，P<0.05）。（2）多巴酚丁胺对照组的AFC为26.6±1.6%，显著高于正常对照组（P<0.05）；多巴酚丁胺治疗组的AFC为20.0±3.9%，显著高于ALI组（P<0.05）。（3）α-rENaC mRNA在ALI组的表达为1.40±0.40，在多巴酚丁胺治疗组的表达为1.38±0.13，均显著高于多巴酚丁胺对照组（1.01±0.14）和正常对照组（0.44±0.11，P均<0.05）。β-rENaC mRNA在ALI组的表达为0.70±0.8，在多巴酚丁胺治疗组的表达为0.71±0.17，均显著高于多巴酚丁胺对照组（0.58±0.12）和正常对照组（0.44±0.11，P均<0.05）。正常对照组与多巴酚丁胺对照组之间，以及ALI组与多巴酚丁胺治疗组之间，α和β-rENaC mRNA的表达无显著差异（P均>0.05）。（4）γ-rENaC mRNA在多巴酚丁胺对照组的表达为0.90±0.19，在多巴酚丁胺治疗组的表达为0.97±0.15，均显著高于正常对照组（0.69±0.10）和ALI组（0.70±0.32）（P均<0.05）。
β-肾上腺素能激动剂能够上调γ-rENaC的表达并改善急性肺损伤中的AFC，可能有利于减轻ALI患者的肺水肿。
