Effect of ergosterol pretreatment on neuronal damage in hippocampal CA1 area of propofol anesthetized rats
10.3760/cma.j.cn115354-20210913-00597
- VernacularTitle:麦角甾醇预处理对丙泊酚麻醉大鼠海马CA1区神经元损伤的影响
- Author:
Yulin ZHU
1
;
Kejun DONG
;
Zhishuai LI
Author Information
1. 烟台市烟台山医院麻醉科，烟台 264001
- Keywords:
Ergosterol;
Propofol;
Hippocampal CA1 area;
Neuronal apoptosis;
Phosphatidylinositol 3-kinase-protein kinase B signaling pathway
- From:
Chinese Journal of Neuromedicine
2022;21(3):249-256
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of ergosterol on neurons in CA1 area of the hippocampus and its mechanism in rats anesthetized with propofol.Methods:Forty-five SD rats were randomly divided into control group, propofol group and propofol+ergosterol group ( n=15). Rats in the control group were injected intraperitoneally with 100 mg/kg fat emulsion solvent; rats in the propofol group were injected intraperitoneally with 50 mg/kg propofol first, and after the righting reflex was restored, they were injected with 50 mg/kg propofol; propofol+ergosterol group was intraperitoneally injected with 30 mg/kg ergosterol, followed by propofol injection, and the propofol injection method was the same as that of the propofol group. Injection was given continuously for 7 d. After the last injection, the rats in each group were awake for 2 h. The ultrastructure of neurons in hippocampal CA1 area was observed by transmission electron microscopy. HE staining, TUNEL and neuronal nuclear antigen (NeuN) staining, and Western blotting were used to detect the morphology, apoptosis, and postsynaptic density protein 95 (PSD95) expression of neurons in the hippocampal CA1 area, respectively. Western blotting was used to determine the expressions of apoptosis-related proteins and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway proteins in hippocampal CA1 area of rats. Results:Transmission electron microscopy and HE staining showed that the damage of neurons in the hippocampal CA1 area of the propofol+ergosterol group was slighter than that of the propofol group. As compared with control group, propofol group had significantly higher neuronal apoptosis, significantly higher levels of activated Caspase 3 and Bax protein expressions, significantly decreased Bcl-2 and PSD95 expressions, significantly increased apoptosis inducing factor (AIF) and Cytochrome (Cyt)-C protein expressions, statistically lower Sirt1 protein expression, and significantly lower phosphorylated (p)-PI3K/PI3K level and p-Akt/Akt ratio in the hippocampal CA1 area ( P<0.05). As compared with propofol group, propofol+ergosterol group had significantly lower neuronal apoptosis in the hippocampal CA1 area (27.33±1.37% vs. 17.47±0.87%, P<0.05). As compared with propofol group, propofol+ergosterol group had significantly lower activated Caspase 3 and Bax protein expressions, significantly increased Bcl-2 and PSD95 expressions, significantly decreased AIF and Cyt-C protein expressions, statistically higher Sirt1 protein expression, and significantly higher p-PI3K/PI3K level and p-Akt/Akt ratio in the hippocampal CA1 area ( P<0.05). Conclusion:Ergosterol pretreatment can inhibit propofol-induced neuron apoptosis and alleviate the neuronal damage in the hippocampal CA1 area, whose mechanism may be mediated by PI3K-Akt signaling pathway.
