Effects Of The Neuronal Protein Damage And Aggregation Induced By Inhaled Anesthetic Sevoflurane In The APP/PS1 Transgenic Mouse Hippocampus

Background: Protein aggregation is one of the major pathologic features associated with degeneration of AD neurons.Studies have shown that protein aggregation such as beta amyloid protein,tau protein and oxidative damage proteins can activate apoptosis-related cascade signaling pathways leading to neuronal apoptosis and exacerbation neuropathic damage of AD.With the intensification of the global aging process,nearly 10 million AD patients received general anesthesia and surgical treatment every year.The study found that general anesthesia is closely related to the development and progression of AD,the commonly used inhaled sevoflurane can induce neuronal apoptosis in hippocampus,cause cognitive impairment and aggravate the pathogenesis of AD,but whether its mechanism is related to the induction of abnormal protein damage and aggregation in hippocampal neurons is unclear.Therefore,to explore the effect of inhalation of sevoflurane on protein damage and protein aggregation in hippocampal neurons,and to provide theoretical basis for the selection of clinical medication and to guide the rational development of anesthesia program in AD patients,which has important scientific and clinical significance.Objective: To investigate effects of the neuronal protein damage and aggregation induced by Inhaled anesthetic sevoflurane in the APP/PS1 transgenic mice hippocampus.Methods: 60 APP/PS1 transgenic mice at the age of 12 months were divided into 2 groups at random(n=30): the blank Control group and sevoflurane group,mice in control group were exposed to continued 2 L/min oxygen for 4 hours,mice in sevoflurane group were exposed to 2% sevoflurane for 4 hours.Mice were killed and dissected 6 hours or 24 hours after anesthesia respectively.TUNEL and DCFH-DA were applied to detect the hippocampal neuronal apoptosis and ROS level respectively,immunohistochemical method and western blot were applied to detect A?42 levels,carbonyl compounds and nitrotyrosine that related to the protein damage,TEM was applied to observe the protein aggregation.Results: Compared with the Control group,the neuronal apoptosis rate,expression levels of ROS,A?42,oxidative protein carbonyl compounds and nitrotyrosine were significantly increased in sevoflurane group(p<0.05).Conclusion : 2% sevoflurane exposure for 4 hours significantly aggravated the oxidative-stress injury of hippocampal neuron,hippocampal protein damage and aggregation,guided neuronal apoptosis,exacerbated neuropathology injury.