Dexmedetomidine regulates mitochondrial autophagy through PINK1/Parkin signaling pathway to improve postoperative cognitive dysfunction in aged rats
Objective To explore the molecular mechanism of dexmedetomidine regulating mitochondrial autophagy through PINKl/Parkin signaling pathway to improve postoperative cognitive dysfunction in aged rats.Methods SD rats were randomly divided into sham group,model group,dexmedetomidine(40 p.g/kg)group,autophagy inhibitor trimethyladenine(3-MA,100 mmol/L)group and dexmedetomidine+3-MA group,with 8 rats in each group.The cognitive ability of rats was detected by the open field and water maze experiments.The apoptosis of hippocampal neurons was detected by TUNEL staining.The autophagy of hippocampal neurons was observed by transmission electron microscopy.The expressions of PTEN-induced kinase 1(PINK1)/Parkinson's disease protein(Parkin),autophagy effect protein Beclin 1,microtubule light chain protein 3B(LC3 Ⅱ/Ⅰ)and mitochondrial autophagy receptor p62(p62)were detected by Western blot.Rseults Dexmedetomidine significantly improved cognitive function,inhibited neuronal apoptosis,improved mitochondrial structure,reduced the number of autophagosomes,increased the expressions of PINK1,Parkin,Beclin 1,LC3 Ⅱ/Ⅰ,and decreased the expression of p62 in aged rats.However,all the above improvement effects of dexmedetomidine were mitigated or inhibited by 3-MA.Conclusion Dexmedetomidine enhances mitochondrial autophagy by activating PINK1/Parkin signaling pathway to improve postoperative cognitive dysfunction in aged rats.
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