Gao Qiu-Shi, Zhang Ya-Han, Xue Hang, Wu Zi-Yi, Li Chang, Zhao Ping
Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Neural Regen Res. 2021 Jun;16(6):1052-1061. doi: 10.4103/1673-5374.300456.
Previous studies have demonstrated that sevoflurane postconditioning can provide neuroprotection after hypoxic-ischemic injury and improve learning and memory function in developing rodent brains. The classical Rice-Vannucci model was used to induce hypoxic-ischemic injury, and newborn (postnatal day 7) rats were treated with 2.4% sevoflurane for 30 minutes after hypoxic-ischemic injury. Our results showed that sevoflurane postconditioning significantly improved the learning and memory function of rats, decreased astrogliosis and glial scar formation, increased numbers of dendritic spines, and protected the histomorphology of the hippocampus. Mechanistically, sevoflurane postconditioning decreased expression of von Hippel-Lindau of hypoxia-inducible factor-1α and increased expression of DJ-1. Injection of 1.52 μg of the hypoxia-inducible factor-1α inhibitor YC-1 (Lificiguat) into the left lateral ventricle 30 minutes before hypoxic-ischemic injury reversed the neuroprotection induced by sevoflurane. This finding suggests that sevoflurane can effectively alleviate astrogliosis in the hippocampus and reduce learning and memory impairments caused by glial scar formation after hypoxic-ischemic injury. The underlying mechanism may be related to upregulated DJ-1 expression, reduced ubiquitination of hypoxia-inducible factor-1α, and stabilized hypoxia-inducible factor-1α expression. This study was approved by the Laboratory Animal Care Committee of China Medical University, China (approval No. 2016PS337K) on November 9, 2016.
先前的研究表明,七氟醚后处理可在缺氧缺血性损伤后提供神经保护,并改善发育中小鼠脑内的学习和记忆功能。采用经典的Rice-Vannucci模型诱导缺氧缺血性损伤,新生(出生后第7天)大鼠在缺氧缺血性损伤后用2.4%七氟醚处理30分钟。我们的结果显示,七氟醚后处理显著改善了大鼠的学习和记忆功能,减少了星形胶质细胞增生和胶质瘢痕形成,增加了树突棘数量,并保护了海马的组织形态学。机制上,七氟醚后处理降低了缺氧诱导因子-1α的von Hippel-Lindau表达,并增加了DJ-1的表达。在缺氧缺血性损伤前30分钟向左侧脑室注射1.52 μg缺氧诱导因子-1α抑制剂YC-1(利福昔呱)可逆转七氟醚诱导的神经保护作用。这一发现表明,七氟醚可有效减轻海马中的星形胶质细胞增生,并减少缺氧缺血性损伤后由胶质瘢痕形成引起的学习和记忆障碍。潜在机制可能与DJ-1表达上调、缺氧诱导因子-1α泛素化减少以及缺氧诱导因子-1α表达稳定有关。本研究于2016年11月9日获得中国医科大学实验动物护理委员会批准(批准号:2016PS337K)。