Wang Shiquan, Li Yuheng, Wei Jinlong, Li Pei, Yang Qianzi
Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Department of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
BMC Anesthesiol. 2018 Nov 17;18(1):171. doi: 10.1186/s12871-018-0636-z.
Sevoflurane preconditioning induces brain ischemic tolerance, but the mechanism remains poorly elucidated. Nitration is an important form of post-translational modification in pathological signaling. This study was to investigate the role of thioredoxin-1 (Trx-1) nitration in neuroprotection effect induced by sevoflurane preconditioning in a transient stroke model in rats.
Adult male Sprague-Dawley rats were preconditioned with 2% sevoflurane or vehicle oxygen exposure, 1 h per day, for 5 consecutive days. At 24 h after the last exposure, rats were subjected to focal brain ischemia induced by middle cerebral artery occlusion (MCAO) for 90 min, followed by 72-h reperfusion. Trx-1 expression and activity, as well as the content of nitrotyrosine at penumbra were detected at 24 h after preconditioning and 2, 8, 24, 72 h after MCAO. Nitrated Trx-1 was examined by immunoprecipitation at 8 h after MCAO. The role of Trx-1 nitration in ischemic tolerance was assessed by administration of nitrated human-Trx-1 prior to MCAO. Neurological scores, brain infarct volumes and TUNEL staining were evaluated at 24 h after reperfusion.
Ischemic stroke decreased Trx-1 activity but not the expression in penumbra tissue. The content of nitrotyrosine was elevated after MCAO. Preconditioning with sevoflurane increased Trx-1 activity and reduced its nitration at 8 h after MCAO in comparison with vehicle preconditioning. The decrement of Trx-1 activity was correlated with its nitration level. Exogenous administration of nitrated human-Trx-1 reversed the brain ischemic tolerance of sevoflurane preconditioning, exacerbating brain infarct volume, neurobehavioral defects and apoptosis, while administration of human-Trx-1 had no effect on the sevoflurane preconditioning-induced neuroprotection.
Ischemic stroke reduces Trx-1 activity via post-translational nitrative modulation in rats. Sevoflurane preconditioning induces brain ischemic tolerance and anti-apoptosis by partially preserving Trx-1 activity via inhibiting nitration.
七氟醚预处理可诱导脑缺血耐受，但其机制仍未完全阐明。硝化作用是病理信号转导中一种重要的翻译后修饰形式。本研究旨在探讨硫氧还蛋白-1（Trx-1）硝化在七氟醚预处理诱导大鼠短暂性脑缺血模型神经保护作用中的作用。
成年雄性Sprague-Dawley大鼠分别用2%七氟醚或空气进行预处理，每天1小时，连续5天。末次暴露后24小时，大鼠接受大脑中动脉闭塞（MCAO）诱导的局灶性脑缺血90分钟，随后再灌注72小时。在预处理后24小时以及MCAO后2、8、24、72小时检测半暗带区Trx-1的表达、活性以及硝基酪氨酸含量。在MCAO后8小时通过免疫沉淀法检测硝化Trx-1。在MCAO前给予硝化人Trx-1评估Trx-1硝化在缺血耐受中的作用。在再灌注24小时后评估神经功能评分、脑梗死体积和TUNEL染色。
缺血性脑卒中降低了半暗带组织中Trx-1的活性，但未改变其表达。MCAO后硝基酪氨酸含量升高。与空气预处理相比，七氟醚预处理可增加MCAO后8小时Trx-1的活性并减少其硝化作用。Trx-1活性的降低与其硝化水平相关。外源性给予硝化人Trx-1可逆转七氟醚预处理的脑缺血耐受，加重脑梗死体积、神经行为缺陷和细胞凋亡，而给予人Trx-1对七氟醚预处理诱导的神经保护作用无影响。
缺血性脑卒中通过翻译后硝化调节降低大鼠Trx-1活性。七氟醚预处理通过抑制硝化作用部分保留Trx-1活性，从而诱导脑缺血耐受和抗凋亡作用。
