雄激素剥夺对油酸诱导急性肺损伤肺泡上皮钠离子通道表达的研究

Effect of androgen depletion on expression of the alveolar ENaC-?琢 in male rats with oleic acid -induced acute lung injury/acute respiratory distress syndrome

摘要:

目的：观察通过手术去势方法降低大鼠体内雄激素水平对急性肺损伤/急性呼吸窘迫综合征（acute lung injury/acute respiratory distress syndrome，ALI/ARDS）肺组织中肺泡上皮钠离子通道?琢亚基（epithelial sodium channel ａlpha-subunit，ENaC-?琢）的影响。方法：20只 Sprague-Dawley（SD）大鼠按随机数字表法分为正常对照组、模型组、假手术模型组、去势手术模型组4组，每组5只。以尾静脉注射油酸（oleic acid，OA）0.15 ml/kg复制ALI/ARDS模型，去势手术模型组和假手术模型组分别于造模前２周（14 d）行开腹双侧睾丸切除术或开腹但不行睾丸切除。于造模成功6 h后行开胸手术，测定肺湿重/干重比值（wet/ery，W/D），用逆转录-聚合酶链反应（reverse transcription-polymerase chain reaction，RT-PCR）和 Western blot测定肺组织中ENaC-?琢 mRNA及蛋白的表达。结果：（1）与正常对照组比较，所有模型组大鼠肺组织病理学改变明显且W/D比值明显增加（模型组与正常对照组，P=0.000；假手术模型组与正常对照组，P=0.000；去势手术模型组与正常对照组，P=0.000）、ENaC-?琢的mRNA和蛋白表达明显降低（ENaC-?琢 mRNA：模型组与正常对照组，P=0.000；假手术模型组与正常对照组，P=0.000；去势手术模型组与正常对照组，P=0.001；ENaC-?琢蛋白：模型组与正常对照组，P=0.000；假手术模型组与正常对照组，P=0.000；去势手术模型组与正常对照组，P=0.045）。（2）与模型组相比，去势手术组大鼠肺组织病理学改变较减轻，W/D比值明显降低（P=0.000）、ENaC-?琢的mRNA和蛋白表达明显上调（ENaC-?琢 mRNA：去势手术模型组与模型组，P=0.002 ；ENaC-?琢蛋白：去势手术模型组vs. 模型组，P=0.030）。结论：在ALI/ARDS发生时，雄激素本身对急性肺损伤时肺泡上皮细胞中ENaC-?琢的表达具有抑制作用，降低体内雄激素水平可以提高肺组织中ENaC-?琢的mRNA和蛋白的表达，降低肺组织水肿程度。

Abstract:

Objective：To study the effect of androgen depletion on expression of alveolar epithelial sodium channel ａlpha-subunit（ENaC-?琢）in male rats with oleic acid （OA）-induced acute lung injury/acute respiratory distress syndrome（ALI/ARDS） by the way of castrating both gonads. Methods：Twenty adult Sprague-Dawley（SD） male rats were randomly divided into control group，OA model group，castrated model group and sham-castrated model group according to the random digits table with 5 rats in each group. The model was copied by the injection of OA（0.15 ml/kg） through tail vein，and the castrated model group and sham-castrated model group were castrated 2 weeks before exposure to OA. After 6 h exposure to OA，the chest was opened to retrieve lung issues，the wet/dry（W/D） ratio was measured and the expression of mRNA and protein of ENaC-?琢 was determined by RT-PCR and Western blot respectively. Results：①The pathological change of lung tissue was distinctive and W/D ratio was significantly increased in all model groups com－pared with those in control group（OA model group vs. control group，P=0.000；sham-castrated model group vs. control group，P=0.000；castrated model group vs. control group，P=0.000）. The expression of mRNA and protein of ENaC-?琢 was significantly lower in model groups than those in normal group（ENaC-?琢 mRNA：OA model group vs. control group，P=0.000；sham-castrated model group vs. control group，P=0.000；castrated model group vs. control group，P=0.001；ENaC-?琢 protein：OA model group vs. control group，P=0.000；sham-castrated model group vs. control group，P=0.000；castrated model group vs.control group，P=0.045）. ②The pathological change of lung tissue was attenuated and W/D ratio was significantly decreased in castrated model group compared with those in OA model group（P=0.000）. The expression of mRNA and protein of ENaC-?琢 in castrated model group was significantly up-regulated compared with that in OA model group（ENaC-?琢 mRNA：castrated model group vs. OA model group，P=0.002；ENaC-?琢 protein：castrated model group vs. OA model group，P=0.030）. Conclusion：Androgen may restrain the expression of ENaC-?琢 in lung issues in male rats with ALI/ARDS.