Midazolam Attenuates Autophagy and Apoptosis Caused by Ketamine by Decreasing Reactive Oxygen Species in the Hippocampus of Fetal Rats
Midazolam Attenuates Autophagy and Apoptosis Caused by Ketamine by Decreasing Reactive Oxygen Species in the Hippocampus of Fetal Rats
复制标题
咪达唑仑通过减少胎鼠海马中的活性氧来减轻氯胺酮引起的自噬和细胞凋亡
DOI：
10.1016/j.neuroscience.2018.03.040
复制
发表时间：
2018-09-15
期刊：
影响因子：
3.3
通讯作者：
Gao, Li
中科院分区：
文献类型：
--
作者：
Li, Yanan;Li, Xinran;Gao, Li
Every year between 0.75% and 2% of pregnant women require surgery that is related to either the pregnancy or other medical problems in USA. Therefore, the neurodegeneration following anesthesia in a variety of animal models has attracted our attention. Neurotoxic effects of ketamine cannot be ignored. In contrast, some anesthetics, including midazolam, protect neurons and increase dendritic spine density. However, the mechanism of neuroprotection by midazolam is not clear, and whether midazolam can relieve the damage caused by ketamine is unknown. Therefore, in this study, we explored the effects of midazolam on ketamine anesthesia. We measured protein levels of cleaved-caspase-3 (c-caspase-3), beclin-1, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), autophagy-related gene 4 (ATG4), ATG5, p62 (SQSTM1), and the autophagy marker light chain 3 (LC3) in hippocampus by Western analysis. We also measured total antioxidant capacity (T-AOC), and levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in hippocampus and PC12 cells. Results showed that ketamine induced apoptosis through activation of the mitochondria! pathway by increasing the expression of c-caspase-3 and Bax, and decreasing the expression of Bcl-2 at the protein level. Ketamine also increased the expression of LC3II and ATG5, proteins, decreased the expression of ATG4 and P62, and finally induced autophagy. Ketamine promoted the production of ROS and MDA, and reduced total antioxidant capacity (T-AOC); these effects were attenuated by midazolam. In conclusion, ketamine induces toxicity in human neurons through ROS-mediated activation of mitochondrial apoptotic pathway and autophagy. The harmful effects of ketamine can be ameliorated by midazolam. (C) 2018 Published by Elsevier Ltd on behalf of IBRO.
