Effects of repeated sevoflurane exposure on hippocampal cell apoptosis and long-term learning and memory ability in neonatal rats

Abstract

Objective: To investigate the effects of repeated sevoflurane exposure on hippocampal cell apoptosis and long-term learning and memory ability in neonatal rats and its regulation on PI3K/AKT pathway. Methods: Ninety SD rats were randomly divided into the control group (25% oxygen), the single exposure group (inhalation of 3% sevoflurane and 25% oxygen on the 6th day after birth), the 3-times exposure group (inhalation of 3% sevoflurane and 25% oxygen on the 6th, 7th, and 8th day after birth), the 5-times exposure group (inhalation of 3% sevoflurane and 25% oxygen on the 6th, 7th, 8th, 9th and 10th day after birth), and the 5-times exposure + 740Y-P (PI3K activator) group (intraperitoneal injection of 0.02 mg/kg 740Y-P after inhalation of sevoflurane for 5 times) according to the random number table method. Morris water maze was used to measure the learning and memory ability; HE staining and transmission electron microscopy were used to observe the morphological and structural changes of neurons in the hippocampus; TUNEL was used to detect the apoptosis of hippocampal nerve cells; Western blot was used to detect the expressions of apoptosis-related proteins (Caspase-3, Bax, Bcl-2) and PI3K/AKT pathway related proteins in the hippocampus of rats. Results: Compared with the control group and the single exposure group, the learning and memory abilities of rats in the 3-times exposure group and the 5-times exposure group were severely reduced, the morphology and structure of hippocampal neurons were severely damaged, and the apoptosis rate of hippocampal nerve cells was increased (P＜0.05), the expressions of Capase-3 and Bax proteins were significantly increased (P＜0.05), and the expressions of Bcl-2 protein and PI3K/AKT pathway protein were significantly decreased (P＜0.05). With the increase in the number of exposures to sevoflurane, the learning and memory abilities of rats were significantly reduced, the hippocampal neuron cells were severely damaged, the hippocampal neuronal apoptosis rate was significantly increased (P＜0.05), and the expressions of PI3K/AKT pathway proteins were significantly reduced (P＜0.05). Compared with the 5-times exposure group, the learning and memory abilities and hippocampal neuron structure of rats in the 5-times exposure +740Y-P group were restored to a certain extent, and the hippocampal neuronal apoptosis rate, the levels of capase-3 and Bax protein were significantly reduced (P＜0.05), while the expressions of Bcl-2 protein and PI3K/AKT pathway protein were increased significantly (P＜0.05). Conclusion: Repeated exposure to sevoflurane can significantly reduce the learning and memory abilities of neonatal rats and exacerbate hippocampal neuronal apoptosis, which may be mediated by inhibiting the PI3K/AKT pathway.