Sipahi Emine Yilmaz, Ozel Tekin Ishak, Comert Mustafa, Barut Figen, Ustun Huseyin, Sipahi Tunc Hakan
Department of Pharmacology, Faculty of Medicine, Karaelmas University, 67100 Incivez Zonguldak, Turkey.
Pharmacol Res. 2004 Dec;50(6):585-91. doi: 10.1016/j.phrs.2004.04.003.
Oxidation of the low-density lipoprotein (LDL) results in the production of modified LDLs. Oxidation of LDL cholesterol plays a role on the pathogenesis of endothelial dysfunction. This study was designed to investigate the possible participation of the oxidative modification of low density lipoprotein in the lung edema induced by alpha-naphthylthiourea (ANTU), which is a well-known noxious chemical agent on the lung endothelium. When ANTU injected intraperitoneally into rats (15 mg kg(-1)), it produced lung edema as indicated by an increase in lung weight/body weight (LW/BW) ratio and pleural effusion (PE) reaching a maximum within 4 h. A significant lung edema was observed 4 h after intraperitoneally injection of alpha-naphthylthiourea when compared with olive oil-injected control rats. On microscopic examination of alpha-naphthylthiourea-treated rats were shown to have severe lung injury, while no change was observed in olive oil-treated control rats. While there were no staining in control lungs, positive oxidized low-density lipoproteins immune-fluorescent staining were observed in lung edema group. Our study showed that oxidized low-density lipoprotein (oxLDL) accumulated in ANTU-induced lung damage. This is the first study in which accumulation of oxLDL molecules in the intact lung tissue were shown by fluorescent immune-staining method in experimental lung edema. The potential role of oxLDL in this pathology are still under investigation.
低密度脂蛋白（LDL）的氧化会导致修饰型LDL的产生。LDL胆固醇的氧化在内皮功能障碍的发病机制中起作用。本研究旨在调查低密度脂蛋白的氧化修饰是否可能参与α-萘基硫脲（ANTU）诱导的肺水肿，α-萘基硫脲是一种众所周知的对肺内皮有毒的化学物质。当向大鼠腹腔注射ANTU（15 mg kg⁻¹）时，会产生肺水肿，表现为肺重量/体重（LW/BW）比值增加和胸腔积液（PE），在4小时内达到最大值。与注射橄榄油的对照大鼠相比，腹腔注射α-萘基硫脲4小时后观察到明显的肺水肿。对α-萘基硫脲处理的大鼠进行显微镜检查显示有严重的肺损伤，而在橄榄油处理的对照大鼠中未观察到变化。对照肺无染色，而在肺水肿组观察到氧化型低密度脂蛋白免疫荧光染色呈阳性。我们的研究表明，氧化型低密度脂蛋白（oxLDL）在ANTU诱导的肺损伤中蓄积。这是首次通过荧光免疫染色法在实验性肺水肿中显示完整肺组织中oxLDL分子蓄积的研究。oxLDL在这种病理过程中的潜在作用仍在研究中。
