Effect of propofol preconditioning on cognitive function and hippocampal neuronal apoptosis in aged mice after splenectomy
10.3760/cma.j.cn371468-20240318-00118
- VernacularTitle:丙泊酚预处理对老年小鼠脾脏切除术后认知功能及海马神经元凋亡的影响
- Author:
Tian GAO
1
;
Tianyu ZHANG
;
Ziming ZHOU
;
Ranran ZHAO
;
Hui XU
Author Information
1. 蚌埠市第一人民医院麻醉科，蚌埠 233000
- Publication Type:Journal Article
- Keywords:
Propofol;
Neuronal damage;
Hippocampus;
Postsynaptic density;
Cell apoptosis;
Cognitive dysfunction
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2024;33(12):1065-1073
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate effects of propofol on cognitive dysfunction and underlying mechanisms after splenectomy in aged mice.Methods:Fifty SPF grade male aged mice were divided into five groups: control group, sham operation group, surgery group, sham operation + propofol group, and surgery + propofol group, with 10 mice in each group. The Morris water maze test was used to assess the learning and memory abilities of mice in each group. The hematoxylin-eosin (HE) staining and TUNEL staining were used to observe the apoptosis of brain neurons.ELISA was performed to measure the expression of inflammatory factors in brain tissues. Transmission electron microscopy was used to observe the structure of hippocampal post-synaptic density. Immunofluorescence was employed to determine the expression of ionized calcium-binding adapter molecule 1 (IBA-1) and postsynaptic density protein-95 (PSD-95) in the hippocampus. Immunohistochemistry was used to measure the expression of microtubule-associated protein tau (tau) in the cortex. The expression of B-cell lymphoma-2 (Bcl-2), recombinant Bcl-2-associated X protein (Bax), and cysteine protease-3 (Caspase-3) was determined using both immunohistochemistry and Western blot. Data were statistically analyzed using SPSS 21.0.For comparisons among multiple groups, the results of Morris water maze experiment were compared by repeated measures ANOVA, while other data comparison was conducted by one-way ANOVA, and pairwise comparisons were conducted using the LSD- t test. Results:The results of the Morris water maze test showed that the interaction effect of time and group on the escape latency of the five groups of mice was significant ( F=95.17, P<0.01). During the spatial navigation test of day 4-6, the escape latency of the surgery group was significantly higher than that of the sham operation group ( P<0.05), while the escape latency of the surgery + propofol group was significantly lower than that of the surgery group and higher than that of sham operation+ propofol group(both P<0.05). In the spatial exploration test, the number of platform crossings, the percentage of the distance traveled in the target quadrant out of the total exploration distance, and the duration spent in the target quadrant were all significantly different among the five groups of mice ( F=27.88, 50.21, 32.04, all P<0.01). These values were all lower in the surgery group compared to the sham operation group (all P<0.05), and higher in the surgery + propofol group compared to the surgery group((2.60±0.66) vs (0.80±0.40); (40.56±1.51)% vs (13.82±3.11)%; (19.25±1.31)s vs (6.12±2.00)s) (all P<0.05).ELISA results showed that the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the brain tissues of the five groups of mice were significantly different ( F=1 017.11, 583.55, 185.35, all P<0.01). The levels of TNF-α, IL-1β and IL-6 in the brain tissues of the surgery + propofol group were all lower than those in the surgery group and higher than that of sham operation+ propofol group (all P<0.05).Transmission electron microscopy results showed that the length, width, and number of synapses in the hippocampal postsynaptic density of the five groups of mice were significantly different ( F=137.06, 55.36, 19.93, all P<0.01), and these values were all higher in the surgery + propofol group compared to the surgery group (all P<0.05).Immunofluorescence results showed that the relative fluorescence intensity of PSD95 and IBA-1 in the hippocampus of the five groups of mice were significantly different ( F=14.33, 38.23, both P<0.01). The relative fluorescence intensity of PSD95 in the hippocampus of the surgery + propofol group was higher than that of the surgery group and lower than that of sham operation+ propofol group (both P<0.05), while the relative fluorescence intensity of IBA-1 in the hippocampus of the surgery + propofol group was lower than that of the surgery group and higher than that of sham operation+ propofol group (both P<0.05).TUNEL results showed that the proportion of positive apoptotic cells in the dentate gyrus (DG) region of the brain tissue of the five groups of mice was significantly different ( F=101.94, P<0.01), and this proportion was lower in the surgery + propofol group compared to the surgery group((72.15±3.71)% vs (82.24±4.40)%) and was higher than that of sham operation+ propofol group((50.64±2.36)%)(both P<0.05).Immunohistochemical and Western blot results showed that the relative expression levels of phosphorylated tau protein, Bcl-2, Bax, and Caspase-3 in the brain tissues of the five groups of mice were significantly different ( F=56.54, 50.48, 23.00, 91.10, all P<0.01). The relative expression levels of phosphorylated tau protein, Bax, and Caspase-3 in the brain tissues of the surgery + propofol group were all lower than those in the surgery group (all P<0.05), while the relative expression level of Bcl-2 was higher in the surgery + propofol group compared to the surgery group ( P<0.05). Conclusion:Propofol pretreatment can significantly alleviate postoperative learning and memory impairments in aged mice, mitigate structural damage to the hippocampal postsynaptic density, and improve postoperative cognitive dysfunction by inhibiting the neuronal apoptosis signaling pathway.
