Guo Haiyun, Peng Zhengwu, Yang Liu, Liu Xue, Xie Yaning, Cai Yanhui, Xiong Lize, Zeng Yi
Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
BMC Anesthesiol. 2017 Sep 5;17(1):124. doi: 10.1186/s12871-017-0420-5.
There are growing concerns that anaesthetic exposure can cause extensive apoptotic degeneration of neurons and the impairment of normal synaptic development and remodelling. However, little attention has been paid to exploring the possible cytotoxicity of inhalation anaesthetics, such as isoflurane, in astrocytes. In this research, we determined that prolonged exposure to an inhalation anaesthetic caused cytotoxicity in astrocytes, and we identified the underlying molecular mechanism responsible for this process.
Astrocytes were exposed to isoflurane, and astrocytic survival was then measured via LDH release assays, MTT assays, and TUNEL staining. TWIK-related potassium (K) channel-1 (TREK-1) over-expression and knockdown models were also created using lentiviruses. The levels of TREK-1 and brain-derived neurotrophic factor (BDNF) were measured via Western blot and qRT-PCR.
Prolonged exposure to isoflurane decreased primary astrocytic viability in a dose- and time-dependent manner. Moreover, with prolonged exposure to isoflurane, the TREK-1 level increased, and the BDNF level was reduced. TREK-1 knockdown promoted the survival of astrocytes and increased BDNF expression following isoflurane exposure.
Overdoses of and prolonged exposure to isoflurane induce cytotoxicity in primary astrocytes. TREK-1 plays an important role in isoflurane-induced cultured astrocytic cytotoxicity by down-regulating the expression of BDNF.
人们越来越担心麻醉暴露会导致神经元广泛的凋亡性退化以及正常突触发育和重塑受损。然而，对于探索吸入性麻醉剂（如异氟烷）对星形胶质细胞可能的细胞毒性却鲜有关注。在本研究中，我们确定长时间暴露于吸入性麻醉剂会导致星形胶质细胞产生细胞毒性，并确定了这一过程的潜在分子机制。
将星形胶质细胞暴露于异氟烷中，然后通过乳酸脱氢酶（LDH）释放测定、MTT测定和TUNEL染色来测量星形胶质细胞的存活率。还使用慢病毒构建了TWIK相关钾（K）通道-1（TREK-1）过表达和敲低模型。通过蛋白质免疫印迹法（Western blot）和定量逆转录聚合酶链反应（qRT-PCR）测量TREK-1和脑源性神经营养因子（BDNF）的水平。
长时间暴露于异氟烷会以剂量和时间依赖性方式降低原代星形胶质细胞的活力。此外，随着长时间暴露于异氟烷，TREK-1水平升高，BDNF水平降低。TREK-1敲低可促进星形胶质细胞的存活，并增加异氟烷暴露后BDNF的表达。
过量和长时间暴露于异氟烷会诱导原代星形胶质细胞产生细胞毒性。TREK-1通过下调BDNF的表达在异氟烷诱导的培养星形胶质细胞毒性中起重要作用。
