右美托咪啶通过PINK1/Parkin信号通路调控线粒体自噬改善老年大鼠术后认知功能障碍
Dexmedetomidine regulates mitochondrial autophagy through PINK1/Parkin signaling pathway to improve postoperative cognitive dysfunction in aged rats
姜美玲 1伦明辉 1黄泽清1
作者信息
- 1. 中国医科大学肿瘤医院 辽宁省肿瘤医院麻醉科,辽宁沈阳 110042
- 折叠
摘要
目的 探究右美托咪啶通过PINK1/Parkin信号通路调控线粒体自噬改善老年大鼠术后认知功能障碍的分子机制.方法 SPF级SD大鼠随机分为假手术组、模型组、右美托咪啶(40 μg/kg)组、自噬抑制剂三甲基腺嘌呤(3-MA,100 mmol/L)组、右美托咪啶+3-MA组,每组8只.旷场和水迷宫实验检测大鼠认知能力;TUNEL染色检测大鼠海马神经元凋亡情况;透射电镜观察大鼠海马神经元自噬情况;Western blot检测各组大鼠脑组织PTEN诱导激酶1(PINK1)/帕金森病蛋白(Parkin)、自噬效应蛋白Beclin 1、微管轻链蛋白3B(LC3 Ⅱ/Ⅰ)、线粒体自噬受体p62(p62)蛋白表达.结果 右美托咪啶显著改善老年大鼠术后认知功能,抑制神经元凋亡,改善线粒体结构,减少自噬小体数量,升高大鼠脑组织PINK1、Parkin、Beclin 1、LC3 Ⅱ/Ⅰ蛋白表达水平,降低p62蛋白表达水平.而右美托咪定的上述改善作用均被3-MA减轻或抑制.结论 右美托咪啶通过激活PINK1/Parkin信号通路增强线粒体自噬改善老年大鼠术后认知功能障碍.
Abstract
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.
关键词
右美托咪啶/认知功能障碍/PINK1/Parkin信号通路/自噬Key words
dexmedetomidine/cognitive dysfunction/PINK1/Parkin signaling pathway/autophagy引用本文复制引用
基金项目
辽宁省自然科学基金(2023-BS-044)
出版年
2024
NETL
NSTL
万方数据