Zhang Yuan-Li, Li Qing-Quan, Guo Wei, Huang Yi, Yang Jiong
Division of Pulmonary Medicine, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, China.
Shock. 2007 Aug;28(2):245-52. doi: 10.1097/SHK.0b013e31803404a9.
Previous studies show that chronic alcohol abuse is an independent risk factor for acute lung injury (ALI) and impairs alveolar epithelial barrier function through glutathione depletion. However, the precise molecular structures that are damaged by chronic ethanol ingestion have not been identified. To test whether chronic ethanol ingestion impairs the alveolar epithelium barrier by tight junction protein deterioration and predisposes to ALI, this study determined the alterations in tight junction proteins occludin, zonula occludens (ZO)-1, and adherens junction protein E-cadherin in alveolar epithelium and observed the protective effect of glutamine (Gln) supplementation. Sixty Sprague-Dawley rats were assigned to control, ethanol (6 weeks' ethanol feeding), lipopolysaccharide ([LPS] 2 mg/kg, i.v.), ethanol plus LPS, ethanol plus Gln (0.3 g/kg, gavage daily), and ethanol plus Gln plus LPS groups. Treatment with both ethanol and LPS significantly increased bronchoalveolar epithelial permeability, and treatment with ethanol plus LPS further increased the permeability. Using immunofluorescence, immunoblotting, and reverse transcriptase-polymerase chain reaction, this study shows that treatment with both ethanol and LPS induced partial breakdown of membrane staining and decreased cytoplasm staining in alveolar epithelium and decreased the messenger RNA and protein expression of those molecules in alveolar epithelial cells. Treatment with ethanol plus LPS caused further deterioration. Moreover, Gln supplementation markedly attenuated the enhanced bronchoalveolar epithelial permeability and decreased messenger RNA and protein expression of those molecules induced by ethanol and ethanol plus LPS. These data suggest that chronic ethanol ingestion impairs the alveolar epithelial barrier function via occludin, ZO-1, and E-cadherin deterioration, and predisposes to ALI. Glutamine supplementation has protective effect.
先前的研究表明，长期酗酒是急性肺损伤（ALI）的一个独立危险因素，且会通过消耗谷胱甘肽损害肺泡上皮屏障功能。然而，长期摄入乙醇所破坏的精确分子结构尚未明确。为了测试长期摄入乙醇是否会因紧密连接蛋白降解而损害肺泡上皮屏障并导致ALI，本研究确定了肺泡上皮中紧密连接蛋白闭合蛋白、闭合小环蛋白（ZO）-1和黏附连接蛋白E-钙黏蛋白的变化，并观察了补充谷氨酰胺（Gln）的保护作用。将60只Sprague-Dawley大鼠分为对照组、乙醇组（乙醇喂养6周）、脂多糖（[LPS] 2 mg/kg，静脉注射）组、乙醇加LPS组、乙醇加Gln组（0.3 g/kg，每日灌胃）以及乙醇加Gln加LPS组。乙醇和LPS联合处理显著增加了支气管肺泡上皮通透性，乙醇加LPS处理则进一步增加了通透性。通过免疫荧光、免疫印迹和逆转录聚合酶链反应，本研究表明，乙醇和LPS联合处理诱导肺泡上皮细胞膜染色部分破坏，细胞质染色减少，并降低了肺泡上皮细胞中这些分子的信使核糖核酸和蛋白质表达。乙醇加LPS处理导致进一步恶化。此外，补充Gln显著减轻了乙醇和乙醇加LPS诱导的支气管肺泡上皮通透性增强，并降低了这些分子的信使核糖核酸和蛋白质表达。这些数据表明，长期摄入乙醇通过闭合蛋白、ZO-1和E-钙黏蛋白的降解损害肺泡上皮屏障功能，并导致ALI。补充谷氨酰胺具有保护作用。
