氯胺酮诱导细胞自噬的研究进展

Research progress of autophagy induced by ketamine

氯胺酮是一种N-甲基-D-天冬氨酸受体(NMDAR)拮抗剂,常作为分离性麻醉剂广泛应用于临床和外科手术中,因其具有较强的致幻效应并使人产生欣快感而在众多娱乐场所中被消遣滥用。此外,氯胺酮还是一种起效迅速的抗抑郁药,对中枢神经系统兼有兴奋和抑制作用,但是长期使用氯胺酮会对中枢神经系统产生较强的神经毒性和精神依赖性。自噬是一个溶酶体依赖性降解蛋白质和细胞器以维持内环境稳态的过程。在氯胺酮诱导神经毒性的过程中,自噬具有双向调控的作用,可加重或减轻机体的神经毒性,但其具体的机制尚不清楚。该文主要从氯胺酮诱导细胞自噬的机制、氯胺酮诱导的自噬与神经毒性的关系以及药物对氯胺酮神经毒性的干预作用等方面进行综述,旨在为进一步研究氯胺酮诱导细胞自噬的机制以及自噬在氯胺酮神经毒性中的调控机制提供参考。

Ketamine is an N-methyl-D-aspartate receptor(NMDAR)antagonist and is commonly used as a discrete anesthetic in clinical and surgical operations.Due to its strong hallucinogenic effect and euphoria,it has been used in many entertainment venues for recreation.In addition,ketamine is a rapidly acting antidepressant with both excitatory and inhibitory effects on the central system.However,long-term use of ketamine will produce strong neurotoxicity and mental dependence on the central nervous system.Autophagy is a process in which proteins and organelles are lysosome-dependently degraded to maintain the homeostasis.In the process of ketamine-induced neurotoxicity,autophagy has a two-way regulation effect(aggravating or reducing the neurotoxicity of the body),but its specific mechanism is not yet clear.This article mainly reviewed the mechanism of ketamine-induced autophagy,the relationship between ketamine-induced autophagy and neurotoxicity,and the effect of drug intervention on ketamine neurotoxicity,aiming to provide a reference for further research on the mechanism of ketamine-induced autophagy and the regulation mechanism of autophagy in ketamine neurotoxicity.