β-肾上腺素能激动剂对大鼠肺泡液体的清除效应

Effect of β-adrenergic agonist on alveolar fluid clearance in rats

目的探讨β-肾上腺素能激动剂对肺泡上皮主动清除液体的效应及相关机制。方法48只清洁级雄性SD大鼠随机数字法分成6个组[正常对照组、多巴酚丁胺组、阿米洛利（特异性钠通道阻滞剂）组、多巴酚丁胺＋阿米洛利组、多巴酚丁胺＋阿替洛尔（高度选择性（1-肾上腺素能阻滞剂）组、多巴酚丁胺＋ICI118,551（高度选择性（2-肾上腺素能阻滞剂）组]。单核素示踪技术测定肺泡液体清除率（AFC）。逆转录聚合酶链反应（RT-PCR）检测肺组织肺泡上皮钠通道（α、β、γ-rENaC）mRNA表达。结果（1）β2-肾上腺素能受体效应显著增加AFC：多巴酚丁胺组、多巴酚丁胺＋阿替洛尔组AFC分别为（26.6±1.6）%和（25.0±4.8）%,显著高于正常对照组[（21.0±3.9）%]和多巴酚丁胺＋ICI118,551组[（21.0±4.8）%]（P〈0.05）。多巴酚丁胺组AFC与多巴酚丁胺＋阿替洛尔组比较,差异无统计学意义（P〈0.05）;正常对照组AFC与多巴酚丁胺＋ICI118,551组比较,差异无统计学意义（P〈0.05）。（2）阿米洛利敏感钠通道显著影响肺泡液体清除：阿米洛利组AFC为（6.0±2.8）%,显著低于正常对照组（P〈0.05）。（3）多巴酚丁胺通过非阿米洛利敏感钠通道途径增加肺泡液体清除：多巴酚丁胺＋阿米洛利组AFC为（10.0±2.3）%,显著高于阿米洛利组（P〈0.05）。（4）多巴酚丁胺上调γ-rENaC表达：多巴酚丁胺组、多巴酚丁胺＋阿替洛尔组的γ-rENaC mRNA表达分别为（0.90±0.19）和（0.90±0.09）,显著高于正常对照组（0.69±0.09）和多巴酚丁胺＋ICI118,551组（0.68±0.06）（P均〈0.05）。多巴酚丁胺组γ-rENaC mRNA表达与多巴酚丁胺＋阿替洛尔组比较,差异无统计学意义（P〈0.05）;正常对照组γ-rENaC mRNA表达与多巴酚丁胺＋ICI118,551组比较,差异无统计学意义（P〈0.05）。各组间α、γ-rENaC mRNA表达比较,差异无统计学意义（P均〈0.05）。（5）阿米洛利抑制多巴酚丁胺上调γ-rENaC表达：多巴酚丁胺＋阿米洛利组γ-rENaC mRNA表达为（0.70±0.14）,显著低于多巴酚丁胺组和多巴酚丁胺＋阿替洛尔组（P均〈0.05）。结论β2-肾上腺素能激动效应增加肺泡液体清除,其机制除与上调肺泡上皮β-rENaC表达有关外,还可能与刺激非阿米洛利敏感钠通道途径有关。

Objective To investigate the effect of β-adrenergic agonist on alveolar fluid clearance （AFC） in ratsand the associated mechanism. Method Forty eight Sprague-Dawley male rats were randomly divided into six groups namely： normal control group, dobutamine group, amiloride group, dobutamine ＋ amiamiloride group, dobutamine ＋ atenolol group and dobutamine ＋ ICI118, 551 group）. Alveolar fluid clearance was measured by single nuclide tracer technique. The α, β, γ-rat epithelial sodium channel （α, β, γ-rENaC） InRNA expressions were measured by reverse transcription-polymerase chain reaction （RT-PCR）. Results （1） AFC of dobutamine group and dobutamine ＋ atenolol group were （26.6 ＋ 1.6）% and （25.0 ＋ 4.8）% respectively; The rates of AFC in avove two groups were significantly higher than those in normal control group （21.0± 3.9）% and dobutamine ＋ ICI 118, 551 group （21.0 ±4.8）% （P〈0.05）. There was not any significant difference in AFC between dobutamine group and dobutanfine ＋ atenolol group （ P 〉 0.05） ; and not significant difference in AFC between normal control group and dobutamine ＋ ICI 118, 551 group （P〉0.05） . （2） AFC in amiloride group was （6.0 ± 2.8） %, which was significantly lower than normal control group （ P 〈 0.05）. （3） AFC in dobutamine ＋ amiloride group was （10.0 ±2.3）%, which was significantly higher than that in amiloride group （P 〈 0.05）. （4） γ-rENaC mRNA expression in dobutamine group and dobutamine ＋ atenolol group were （0.90 ±0. 19） and （0.90± 0.09） respectively, which were significantly higher than those in normal control group （0.69 ±0.09） and dobutamine ＋ ICI 118, 551 group （0.68 ± 0.06） （P 〈 0.05）. There was not any significant difference in γ-rENaC mRNA expression between dobutamine group and dobutamine ＋ atenolol group; and not significant difference in γ-rENaC mRNA expression between normal control group and dobutamine ＋ ICI 118, 551 group （P 〉 0.05）. There was not any significant difference in ct, γ-rENaC mRNA expressions between these groups （P〉 0.05） . （5） 7-rENaC mRNA expression in dobutamine ＋ amiloride group was （0.70 ± 0. 14）, which was significantly lower than that in dobutamine group and dobutamine ＋ atenolol group （ P 〈 0.05）. Coladuslon Beta2-adrenergic activation upregulates γ-rENaC expression and also stimulates amiloride-insensitive sodium channel （NaC） pathway to improve AFC in rats.