Effect of matrine on sevoflurane-induced mitochondrial autophagy in neonatal rats by regulating the AMPK/mTOR/ULK1 signaling pathway
Objective To investigate the effect of matrine on sevoflurane-induced mitochondrial autophagy in neonatal rats by regulating the AMP-activated protein kinase/mechanistic target of rapamycin/UNC-52-like kinase 1(AMPK/mTOR/ULK1)signaling pathway.Methods Newborn rats were randomly divided into control group,sevoflurane group,sevoflurane+low-dose matrine group,sevoflurane+high-dose matrine group and sevoflurane+high-dose matrine+Compound C(AMPK inhibitor)group.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of TNF-α,IL-6,and IL-1β.Hematoxylin and eosin(H&E)staining was applied to observe the damage of hippocampal tissue.TTC staining was applied to detect the area of cerebral infarction in rats.TUNEL staining was applied to detect the apoptotic rate of brain cells.Transmission electron microscopy(TEM)was applied to observe mitochondrial autophagy.Western Blot was applied to detect protein levels of autophagic proteins LC3 Ⅱ,LC3 Ⅰ,Park,PINK1,p62,and proteins involved in the AMPK/mTOR/ULK1 signaling pathway in rats.Results Compared with those of control group,rats in sevoflurane group presented significantly damaged hippocampal neurons,significantly higher serum TNF-α,IL-6 and IL-1 β,apoptotic rate in brain cells,cerebral infarction area and protein level of p62,but significantly lower numbers of autophagosomes and autophagic lysosomes and protein levels of Parkin,PINK1,LC3 Ⅱ/LC3 Ⅰ,p-AMPK/AMPK,p-mTOR/mTOR and p-ULK1/ULK1(P＜0.05).Compared with those of sevoflurane group,rats in sevoflurane+low-dose matrine group,sevoflurane+high-dose matrine group presented significantly alleviated hippocampal neuron damages,significantly lower serum TNF-α,IL-6 and IL-1 β,apoptotic rate in brain cells,cerebral infarction area and protein level of p62,but higher numbers of autophagosomes and autophagic lysosomes and protein levels of Parkin,PINK1,LC3 Ⅱ/LC3,p-AMPK/AMPK,p-mTOR/mTOR and p-ULK1/ULK1(P＜0.05).AMPK inhibitor Compound C reversed the protective effect of matrine on neurons of neonatal rats.Conclusion Matrine enhances mitochondrial autophagy level by activating the AMPK/mTOR/ULK1 signaling pathway,thereby alleviating sevoflurane-induced neuronal apoptosis and inflammatory response in neonatal rats.
matrineAMP-activated protein kinase/Mechanistic target of rapamycin/UNC-52-like kinase 1(AMPK/mTOR/ULK1)signaling pathwaysevofluranemitochondrial autophagy
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维普
