Li Qin, Bi Ming Jun, Bi Wei Kang, Kang Hai, Yan Le Jing, Guo Yun-Liang
Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Shandong, 264000, People's Republic of China.
Department of Clinical Medicine, Qingdao University Medical College, Qingdao Shandong, 266003, People's Republic of China.
Environ Toxicol. 2016 Mar;31(3):372-9. doi: 10.1002/tox.22052. Epub 2014 Oct 28.
Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO-1 and Nrf-2 proteins were found in normal brain tissue. CO poisoning could activate HO-1/Nrf-2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning.
急性一氧化碳（CO）中毒是全球中毒致死的最常见原因，可能导致神经病理学和神经生理学改变。急性脑损伤和迟发性脑病是最严重的并发症，但其发病机制尚不清楚。本研究旨在评估依达拉奉对急性CO中毒后细胞凋亡和氧化应激的神经保护作用。通过在高压氧舱中暴露于CO建立大鼠CO中毒模型。用透射电子显微镜（TEM）观察超微结构变化。采用TUNEL染色评估细胞凋亡。用免疫组织化学和免疫荧光双重染色评估血红素加氧酶-1（HO-1）和核因子红细胞2相关因子2（Nrf-2）蛋白的表达水平及其关系。通过动态监测血液中碳氧血红蛋白（HbCO）水平，成功建立了重度CO中毒大鼠模型。CO中毒后可观察到超微结构变化，包括染色质浓缩、细胞质溶解、空泡形成、核膜和细胞器分解。依达拉奉可改善超微结构损伤。CO中毒可诱导细胞凋亡。凋亡细胞广泛分布于皮质、纹状体和海马体。与中毒组相比，依达拉奉治疗可减轻神经元凋亡（P < 0.01）。正常脑组织中可检测到HO-1和Nrf-2蛋白的基础表达。CO中毒可激活HO-1/Nrf-2通路，启动氧化应激反应。给予依达拉奉后，HO-1和Nrf-2的表达显著增加（P < 0.01）。这些结果表明，依达拉奉可能抑制细胞凋亡，激活Keapl-Nrf/ARE通路，从而改善急性CO中毒后的超微结构损伤和神经生理学改变。
