Increased Reabsorption of Alveolar Edema Fluid in the Obese Zucker Rat
Increased Reabsorption of Alveolar Edema Fluid in the Obese Zucker Rat
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DOI：
10.1620/tjem.216.223
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发表时间：
2008-11-01
影响因子：
2.2
通讯作者：
Sakuma, Tsutomu
中科院分区：
文献类型：
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作者：
Ma, Gang;Zhao, Xitong;Sakuma, Tsutomu
糖尿病患者急性呼吸窘迫综合征的发生率降低，但其发病机制尚不清楚。肺泡水肿液的重吸收（肺泡液清除）被认为在急性呼吸窘迫综合征的治疗中起重要作用。然而，对糖尿病的肺泡液清除知之甚少。由于肥胖的Zucker大鼠被用作糖尿病的实验模型，我们确定肥胖的Zucker大鼠的肺泡液清除率是否增加。首先，我们比较了肥胖Zucker大鼠与瘦Zucker大鼠和SD大鼠的肺泡液清除率。然后，我们确定了钠通道、Na、k - atp酶和β(2)-肾上腺素能受体在肥胖Zucker大鼠中的作用，该受体驱动肺泡液清除。肺泡液清除率通过孤立肺中肺泡白蛋白浓度的逐渐增加来估计。我们发现肥胖Zucker大鼠的基底肺泡液清除率是瘦Zucker大鼠和SD大鼠的两倍。肥胖Zucker大鼠α(1)-、β (1)- na、k - atp酶和β(2)-肾上腺素能受体mRNA表达增加，但钠通道mRNA表达不增加。选择性β(2)-腺苷能拮抗剂，而不是Na， k - atp酶抑制剂，特异性地抑制肥胖Zucker大鼠肺泡液清除率的增加。这些结果表明β(2)-肾上腺素能受体的过度表达主要增加肥胖Zucker大鼠的肺泡液清除率。我们推测刺激肺泡液清除可改善糖尿病患者的急性呼吸窘迫综合征。
Diabetic patients have a decreased incidence of acute respiratory distress syndrome, but the mechanism responsible for the decreased incidence is uncertain. Reabsorption of alveolar edema fluid (alveolar fluid clearance) has been considered to play an important role in resolution of acute respiratory distress syndrome. However, little is known regarding alveolar fluid clearance in diabetes mellitus. Since the obese Zucker rat has been used as an experimental model for diabetes mellitus, we determined if alveolar fluid clearance increased in the obese Zucker rat. First, we compared alveolar fluid clearance in obese Zucker rats with that in lean Zucker rats and Sprague-Dawley (SD) rats. Then, we determined the role of sodium channel, Na,K-ATPase, and beta(2)-adrenoceptor, which drives alveolar fluid clearance, in obese Zucker rats. Alveolar fluid clearance was estimated by the progressive increase in alveolar albumin concentrations in the isolated lungs. We found that basal alveolar fluid clearance in obese Zucker rats was two-fold greater than that in lean Zucker rats and SD rats. The mRNA expression of alpha(1)-, beta(1)-Na, K-ATPase and beta(2)-adrenoceptor, but not mRNA expression of sodium channel, increased in obese Zucker rats. A selective beta(2)-agrenergic antagonist, but not a Na, K-ATPase inhibitor, specifically inhibited the increase in alveolar fluid clearance in obese Zucker rats. These results indicate that overexpression of beta(2)-adrenoceptor primarily increases basal alveolar fluid clearance in the obese Zucker rat. We speculate that the stimulation of alveolar fluid clearance ameliorates acute respiratory distress syndrome in patients with diabetes mellitus.