Abstract：Objective: To investigate the effect of midazolam (MDZL) on sevoflurane-induced cognitive impairment in elderly rats by regulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Methods: Elderly rats were randomly divided into sevoflurane group, low (MDZL-L), medium (MDZL-M) and high concentration (MDZL-H) group, MDZL-H+PI3K inhibitor BKM120 (MDZL-H+BKM120) group and control group, with 12 rats in each group. Morris water maze experiment was performed to detect the escape latency, target quadrant swimming time, and number of crossing platforms. Hematoxylin and eosin (H&E) staining was applied to detect the pathology of hippocampal tissue. Immunohistochemical staining was used to detect the proportion of PSD-95 and brain-derived neurotrophic factor (BDNF) positive cells in hippocampal tissue. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was conducted to detect neuronal apoptosis. Western blot was applied to detect B-cell lymphoma 2 (Bcl-2), Bcl-2-associated x (Bax), PI3K, p-PI3K, AKT and p-AKT proteins. Results: Compared with those of the control group, rats of sevoflurane group showed nuclear enlargement and nuclear chromatin aggregation in hippocampal neurons, significantly decreased neurons number, prolonged escape latency, reduced target quadrant swimming time and crossing platforms number, decreased proportions of PSD-95 and BDNF positive cells, and Bcl-2 protein, p-PI3K/PI3K and p-AKT/AKT levels, increased apoptosis rate of neurons and Bax protein in hippocampal tissue (P<0.05). Compared with those of the sevoflurane group, rats of MDZL-L, MDZL-M, and MDZL-H group had significantly shortened escape latency, increased target quadrant swimming time and crossing platforms number, increased proportion of PSD-95, BDNF positive cells, Bcl-2 protein, p-PI3K/PI3K and p-AKT/AKT levels, and decreased apoptosis rate and Bax protein, showing a dose-dependent manner (P<0.05). Pathological damage to hippocampus was alleviated. Compared with those of the MDZL-H group, rats of MDZL-H+BKM120 group presented significantly prolonged escape latency, reduced target quadrant swimming time and crossing platforms number, decreased proportion of PSD-95 and BDNF positive cells, Bcl-2 protein, p-PI3K/PI3K and p-AKT/AKT levels, and increased apoptosis rate of neurons and Bax protein (P<0.05). The pathological injury of hippocampus was aggravated. Conclusion: MDZL may improve sevoflurane-induced cognitive impairment in elderly rats by activating the PI3K/AKT signaling pathway, thereby exerting neuroprotective effects.
2025, Vol. 31 
冀公网安备13080202000677号