Koksel Oguz, Yildirim Caglar, Cinel Leyla, Tamer Lulufer, Ozdulger Ali, Bastürk Mine, Degirmenci Ulas, Kanik Arzu, Cinel Ismail
Department of Thoracic Surgery, Mersin University, School of Medicine, 33079 Mersin, Turkey.
Pharmacol Res. 2005 May;51(5):453-62. doi: 10.1016/j.phrs.2004.11.007.
The objective of this study was to investigate the effects of 3-aminobenzamide (3-AB) on tissue damage in lung after hind limb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Thirty-five adult Wistar rats were divided into five groups. After application of anaesthesia both hind limbs were occluded with tourniquets. Following ischemia period for 60 min, the tourniquets were removed allowing reperfusion for 120 min. The IR group received 0.5 ml of saline while the IR+AB group received 3-AB (10 mgkg(-1) intraperitoneally). The IR+DMSO group was given 0.5 ml 10% DMSO 30 min before the removal of the tourniquets. The control group received 0.5 ml saline and the AB group received 0.5 ml 3-AB (10 mgkg(-1)) intraperitoneally. At the end of the reperfusion period, mid-line sternotomy was performed. Blood samples were taken with cardiac puncture. Bronchoalveolar lavage (BAL) of the left lung was performed with saline. Right lung was preserved for histopathological evaluation and biochemical examination. Lung tissue malondialdehyde (MDA) and 3-nitrotyrosine levels, myeloperoxidase and Na+/K+ ATP-ase activities, wet to dry weight ratios, and plasma and BAL fluid MDA levels were determined. Histopathological evaluation was performed, too. Hind limb IR caused significant increase in the lung tissue 3-NT to total tyrosine ratio (p = 0.014), wet to dry weight ratio (p = 0.000), MPO activity (p = 0.000), and MDA levels (p = 0.000). The animals treated with 3-AB showed a statistically significant decrease in these values (p < 0.05). Na+/K+ ATP-ase activity which was found to be decreased significantly with IR, returned to near normal levels with 3-AB treatment. Additionally, lung tissue injury in IR group characterized with moderate interstitial congestion and neutrophil infiltration, showed remarkable amelioration following 3-AB treatment. Our results strongly support the view that poly(ADP-ribose) polymerase (PARP) plays an important role in the inflammatory process in hind limb I/R-induced lung injury and as a PARP inhibitor, 3-AB seems to have a potential to treat this inflammatory injury.
本研究的目的是通过评估血液生化检测和组织病理学分析，探讨3-氨基苯甲酰胺（3-AB）对后肢缺血再灌注（I/R）后肺组织损伤的影响。将35只成年Wistar大鼠分为五组。麻醉后，用止血带阻断双后肢血流。缺血60分钟后，松开止血带进行120分钟的再灌注。I/R组给予0.5 ml生理盐水，而I/R+AB组给予3-AB（10 mg/kg腹腔注射）。I/R+DMSO组在松开止血带前30分钟给予0.5 ml 10%二甲基亚砜（DMSO）。对照组给予0.5 ml生理盐水，AB组腹腔注射0.5 ml 3-AB（10 mg/kg）。再灌注期结束时，行胸骨正中切开术。通过心脏穿刺采集血样。用生理盐水对左肺进行支气管肺泡灌洗（BAL）。保留右肺用于组织病理学评估和生化检查。测定肺组织丙二醛（MDA）和3-硝基酪氨酸水平、髓过氧化物酶和Na+/K+ ATP酶活性、湿重与干重比值以及血浆和BAL液中MDA水平。同时进行组织病理学评估。后肢I/R导致肺组织3-NT与总酪氨酸比值显著升高（p = 0.014）、湿重与干重比值显著升高（p = 0.000）、MPO活性显著升高（p = 0.000）以及MDA水平显著升高（p = 0.000）。用3-AB治疗的动物这些值有统计学意义的降低（p < 0.05）。发现I/R导致显著降低的Na+/K+ ATP酶活性，经3-AB治疗后恢复到接近正常水平。此外，I/R组以中度间质充血和中性粒细胞浸润为特征的肺组织损伤，经3-AB治疗后有显著改善。我们的结果有力地支持了以下观点：聚（ADP-核糖）聚合酶（PARP）在下肢I/R诱导的肺损伤炎症过程中起重要作用，作为一种PARP抑制剂），3-AB似乎有治疗这种炎症损伤的潜力。
