The role and mechanism of MPTP in sevoflurane-induced hippocampal neuron damage in rats
10.19405/j.cnki.issn1000-1492.2022.06.016
- Author:
Tingting Qiang
1
;
Li Zhang
1
;
Xianwen Hu
1
Author Information
1. Key Laboratory of Aneathesiology and Perioperative Medicine of Anhui Higher EducationInstitutes, Anhui Medical University, Hefei 230601; Dept of Anesthesiology and PerioperativeMedicine, The Second Affiliated Hospital of Anhui Medical University, Hefi 230601
- Publication Type:Journal Article
- Keywords:
sevoflurane;
hippocampal neurons;
cyclosporin A :cyclophilin D;
mitochondrial permeability transition pore
- From:
Acta Universitatis Medicinalis Anhui
2022;57(6):932-938
- CountryChina
- Language:Chinese
-
Abstract:
Abstract:To investigate the role and mechanism of mitochondrial permeability transition pore(MPTP) in the damage of hippocampal neurons in SD rats induced by exposure for 6 hours to sevoflurane.
Methods:The hippocampal neurons of primary cultured SD rats and fetal rats were randomly divided into control group(Con group), cyclosporin A group(CsA group, 0.1,0.5,1 μmol/L), 3% sevoflurane exposure for 6 h Group(Sevo group), cyclosporin A pretreatment+3% sevoflurane 6 h group(Sevo+CsA group, 0.1, 0.5, 1 μmol/L). CCK-8 kit was used to detect cell activity, TUNEL staining was used to detect neuron apoptosis, JC-1 kit was used to detect mitochondrial membrane potential, Calcein AM was used to detect MPTP opening degree, and Western blot was used to detect proteins expression of brain-derived neurotrophic factor(BDNF), postsynaptic compact protein(PSD-95), Snaptophysin, Snapsin-1, and Cyclophilin D(CypD).
Results:Compared with Con group, the cell viability of Sevo group was significantly reduced(P<0.05), the apoptosis rate of neurons increased(P<0.01),the expression of synapse proteins decreased(P<0.05), the mitochondrial membrane potential decreased(P<0.01), the opening degree of MPTP increased(P<0.01), and the expression of CypD protein increased(P<0.01). Cyclosporin A, a specific inhibitor of MPTP opening, could reduce hippocampal neuron apoptosis and synaptic damage caused by sevoflurane exposure, maintain mitochondrial membrane potential, and inhibit MPTP opening and CypD protein expression.
Conclusion:Prolonged exposure to sevoflurane can cause damage to hippocampal neurons in SD rats. The mechanism is related to the promotion of CypD-mediated MPTP opening.
- Full text:2025022114505975549MPTP在七氟烷诱导大鼠海...神经元损伤中的作用及其机制_强婷婷.pdf