Department of Anesthesiology, China Medical University Hospital & College of Medicine, China Medical University, Taichung, Taiwan.
J Trauma Acute Care Surg. 2012 Mar;72(3):660-70. doi: 10.1097/TA.0b013e3182318551.
Traumatic hemorrhagic shock and subsequent resuscitation may promote bacteria translocation and cause endotoxemia, a two-hit process that will induce severe lung injury. The pathogenesis involves oxidative stress, neutrophil infiltration, and inflammatory response. Platonin, a potent antioxidant, possesses potent anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury in a two-hit model of traumatic hemorrhage/resuscitation and subsequent endotoxemia.
Adult male rats were randomized to receive traumatic hemorrhage/resuscitation plus lipopolysaccharide (HS/L) alone or HS/L plus platonin (200 μg/kg; n = 12 in each group). Sham groups were used simultaneously. At 6 hours after resuscitation, rats were killed and the levels of lung injury were assayed.
Rats treated with HS/L alone had severe lung injury as evidenced by significant alterations in lung function (i.e., arterial blood gas and alveolar-arterial oxygen difference) and histology. Significant increases in polymorphonuclear leukocytes/alveoli ratio (neutrophil infiltration index) and significant increases in the concentrations of inflammatory molecules (including chemokine, cytokine, and prostaglandin E2) and malondialdehyde (lipid peroxidation index) revealed that HS/L caused significant oxidative stress, neutrophil infiltration, and inflammatory response in rat lungs. Moreover, our data revealed that the levels of functional and histologic alteration as well as polymorphonuclear leukocytes/alveoli ratio and the concentrations of inflammatory molecules and malondialdehyde in rats treated with HS/L plus platonin (200 μg/kg) were significantly lower than those treated with HR/L alone.
Platonin mitigates lung injury in a two-hit model of traumatic hemorrhage/resuscitation and endotoxemia in rats.
创伤性失血性休克及随后的复苏可能会促进细菌易位，并引起内毒素血症，这是一种双重打击过程，会导致严重的肺损伤。其发病机制涉及氧化应激、中性粒细胞浸润和炎症反应。普拉托宁是一种有效的抗氧化剂，具有强大的抗炎能力。我们试图阐明普拉托宁是否可以减轻创伤性失血性休克/复苏和随后内毒素血症的双重打击模型中的急性肺损伤。
成年雄性大鼠随机接受创伤性失血性休克/复苏加脂多糖（HS/L）单独治疗或 HS/L 加普拉托宁（200μg/kg；每组 12 只）治疗。同时设立假手术组。复苏后 6 小时处死大鼠，检测肺损伤程度。
单独接受 HS/L 治疗的大鼠肺功能（即动脉血气和肺泡-动脉氧差）和组织学均发生明显改变，表明其肺损伤严重。多形核白细胞/肺泡比（中性粒细胞浸润指数）显著增加，炎症分子（包括趋化因子、细胞因子和前列腺素 E2）和丙二醛（脂质过氧化指数）浓度显著升高，表明 HS/L 导致大鼠肺部发生明显的氧化应激、中性粒细胞浸润和炎症反应。此外，我们的数据还表明，与单独接受 HS/L 治疗的大鼠相比，接受 HS/L 加普拉托宁（200μg/kg）治疗的大鼠的功能和组织学改变水平、中性粒细胞浸润指数以及炎症分子和丙二醛浓度均显著降低。
普拉托宁可减轻创伤性失血性休克/复苏和内毒素血症大鼠的肺损伤。
