Melatonin attenuates neurogenic pulmonary edema via the regulation of inflammation and apoptosis after subarachnoid hemorrhage in rats
Melatonin attenuates neurogenic pulmonary edema via the regulation of inflammation and apoptosis after subarachnoid hemorrhage in rats
复制标题
褪黑激素通过调节大鼠蛛网膜下腔出血后的炎症和细胞凋亡减轻神经源性肺水肿
DOI：
10.1111/jpi.12278
复制
发表时间：
2015-11-01
影响因子：
10.3
通讯作者：
Chen, Gao
中科院分区：
文献类型：
--
作者：
Chen, Jingyin;Qian, Cong;Chen, Gao
神经源性肺水肿（NPE）是一种严重的非神经系统并发症，可发生在蛛网膜下腔出血（SAH）后，并与生存率降低和神经系统结局不良相关。褪黑激素是一种强抗氧化剂，对大鼠SAH具有有益作用，包括降低死亡率和减少神经功能缺损。然而，SAH模型中这些临床效应的分子机制尚未明确。本研究采用雄性Sprague道利大鼠蛛网膜下腔出血（SAH）模型，观察褪黑素对SAH诱导的NPE的影响，并探讨其作用机制。在SAH诱导后2小时通过腹膜内注射给予褪黑激素（150 mg/kg）或载体。在SAH后24小时提取肺样品。结果表明，褪黑激素治疗通过抑制紧密连接蛋白（ZO-1和occludin）的破坏来防止肺泡-毛细血管屏障功能障碍，从而减弱了SAH诱导的NPE。此外，治疗下调了成熟白细胞介素（IL）-1，髓过氧化物酶（MPO）和基质金属肽酶（MMP）9的表达/活化水平，这些表达/活化在肺中增加;褪黑激素治疗还改善了神经功能缺损。此外，褪黑激素治疗显着减少caspase-3活性和TUNEL阳性细胞在肺中的数量。总而言之，这些研究结果表明，给予褪黑激素可以通过抑制炎症反应和SAH后的抗细胞凋亡作用来预防肺泡毛细血管屏障功能障碍，从而减轻NPE。
Neurogenic pulmonary edema (NPE) is a serious non-neurological complication that can occur after a subarachnoid hemorrhage (SAH) and is associated with decreased survival and a poor neurological outcome. Melatonin is a strong antioxidant that has beneficial effects against SAH in rats, including reduced mortality and reduced neurological deficits. The molecular mechanisms underlying these clinical effects in the SAH model, however, have not been clearly identified. This study was undertaken to determine the influence of melatonin on SAH-induced NPE and the potential mechanism of these effects using the filament perforation model of SAH in male Sprague Dawley rats. Either melatonin (150 mg/kg) or a vehicle was given via an intraperitoneal injection 2 hr after an SAH induction. Lung samples were extracted 24 hr after SAH. The results show that the melatonin treatment attenuated SAH-induced NPE by preventing alveolar-capillary barrier dysfunctions via inhibiting the disruption of tight junction proteins (ZO-1 and occludin). Moreover, the treatment downregulated the levels of mature interleukin (IL) -1, myeloperoxidase (MPO), and matrix metallopeptidase (MMP) 9 expression/activation, which were increased in the lung; also, melatonin treatment improved neurological deficits. Furthermore, the melatonin treatment markedly reduced caspase-3 activity and the number of TUNEL-positive cells in the lung. Taken together, these findings show that administration of melatonin attenuates NPE by preventing alveolar-capillary barrier dysfunctions via repressing the inflammatory response and by anti-apoptosis effects after SAH.