Dong Wen-Wen, Zhang Yun-Qian, Zhu Xiao-Yan, Mao Yan-Fei, Sun Xue-Jun, Liu Yu-Jian, Jiang Lai
School of Kinesiology, Shanghai University of Sport, Shanghai, China (mainland).
Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China (mainland).
Med Sci Monit. 2017 May 19;23:2357-2364. doi: 10.12659/msm.900452.
BACKGROUND Fibrotic change is one of the important reasons for the poor prognosis of patients with acute respiratory distress syndrome (ARDS). The present study investigated the effects of hydrogen-rich saline, a selective hydroxyl radical scavenger, on lipopolysaccharide (LPS)-induced pulmonary fibrosis. MATERIAL AND METHODS Male ICR mice were divided randomly into 5 groups: Control, LPS-treated plus vehicle treatment, and LPS-treated plus hydrogen-rich saline (2.5, 5, or 10 ml/kg) treatment. Twenty-eight days later, fibrosis was assessed by determination of collagen deposition, hydroxyproline, and type I collagen levels. Development of epithelial-to-mesenchymal transition (EMT) was identified by examining protein expressions of E-cadherin and α-smooth muscle actin (α-SMA). Transforming growth factor (TGF)-β1 content, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content, catalase (CAT), and superoxide dismutase (SOD) activity were determined. RESULTS Mice exhibited increases in collagen deposition, hydroxyproline, type I collagen contents, and TGF-β1 production in lung tissues after LPS treatment. LPS-induced lung fibrosis was associated with increased expression of α-SMA, as well as decreased expression of E-cadherin. In addition, LPS treatment increased MDA levels but decreased T-AOC, CAT, and SOD activities in lung tissues, indicating that LPS induced pulmonary oxidative stress. Hydrogen-rich saline treatment at doses of 2.5, 5, or 10 ml/kg significantly attenuated LPS-induced pulmonary fibrosis. LPS-induced loss of E-cadherin in lung tissues was largely reversed, whereas the acquisition of α-SMA was dramatically decreased by hydrogen-rich saline treatment. In addition, hydrogen-rich saline treatment significantly attenuated LPS-induced oxidative stress. CONCLUSIONS Hydrogen-rich saline may protect against LPS-induced EMT and pulmonary fibrosis through suppressing oxidative stress.
背景 纤维化改变是急性呼吸窘迫综合征（ARDS）患者预后不良的重要原因之一。本研究探讨了选择性羟自由基清除剂富氢盐水对脂多糖（LPS）诱导的肺纤维化的影响。
材料与方法 将雄性ICR小鼠随机分为5组：对照组、LPS处理加溶剂处理组、LPS处理加富氢盐水（2.5、5或10 ml/kg）处理组。28天后，通过测定胶原沉积、羟脯氨酸和I型胶原水平评估纤维化情况。通过检测E-钙黏蛋白和α-平滑肌肌动蛋白（α-SMA）的蛋白表达来确定上皮-间质转化（EMT）的发生情况。测定转化生长因子（TGF）-β1含量、总抗氧化能力（T-AOC）、丙二醛（MDA）含量、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性。
结果 LPS处理后，小鼠肺组织中胶原沉积、羟脯氨酸、I型胶原含量和TGF-β1生成增加。LPS诱导的肺纤维化与α-SMA表达增加以及E-钙黏蛋白表达降低有关。此外，LPS处理增加了肺组织中MDA水平，但降低了T-AOC、CAT和SOD活性，表明LPS诱导了肺氧化应激。2.5、5或10 ml/kg剂量的富氢盐水处理显著减轻了LPS诱导的肺纤维化。富氢盐水处理在很大程度上逆转了LPS诱导的肺组织中E-钙黏蛋白的丢失，而α-SMA的获得则显著减少。此外，富氢盐水处理显著减轻了LPS诱导的氧化应激。
结论 富氢盐水可能通过抑制氧化应激来预防LPS诱导的EMT和肺纤维化。
