葫芦巴碱通过Pink1/Parkin信号通路介导线粒体自噬对OGD/R诱导的神经元凋亡的影响

doi:10.3969/j.issn.1006-6233.2023.05.03

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Abstract Objective: To investigate the impact of trigonelline on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal apoptosis mediated by mitophagy via PTEN-inducible kinase protein 1 (Pink1)/E3 ubiquitin ligase (Parkin) signaling pathway. Methods: Primary cultured rat hippocampal neurons were induced neuronal damage through OGD/R after pretreatment with down-regulation of Pink1 or trigonelline. There were control group, OGD/R group, trigonelline group, pLKO empty vector group (transfected with pLKO empty vector), pLKO-Pink1 group (transfected with pLKO vector connected with Pink1 shRNA interference plasmid), and trigonelline + pLKO-Pink1 group in the experiment. Annexin V-FITC/PI double staining method was used to determine the apoptosis rate of neurons; the mitochondrial membrane potential (MMP) was measured by JC-1 method; Calcein-AM method was used to measure the opening degree of mitochondrial membrane permeability transition pore (MPTP); the number of autophagosomes was observed by transmission electron microscope; Western Blot was used to determine the expression of mitophagy-related proteins [microtubule-associated protein 1 light chain 3 II (LC3 II), Pink1, Parkin]. Results: Compared with the control group, the neuron apoptosis rate and MPTP opening degree in the OGD/R group increased, MMP decreased, the number of autophagosomes and the expression of LC3-II, Pink1 and Parkin proteins increased (P<0.05); compared with the OGD/R group, the neuron apoptosis rate and MPTP opening degree of trigonelline group decreased, MMP increased, the number of autophagosomes and the expression of LC3-II, Pink1 and Parkin proteins increased (P<0.05), the trends of pLKO-Pink1 group were opposite to those of trigonelline group; compared with the trigonelline group, the neuron apoptosis rate and MPTP opening degree in the trigonelline+pLKO-Pink1 group increased, MMP decreased, the number of autophagosomes and the protein expressions of LC3-II, Pink1 and Parkin decreased (P<0.05). Conclusion: Trigonelline can inhibit OGD/R-induced neuronal apoptosis, which may be achieved by activating Pink1/Parkin signaling pathway and up-regulating mitophagy.

Key words： Trigonelline Oxygen-glucose deprivation/reoxygenation injury Pink1/Parkin signaling pathway Mitophagy Neurons Apoptosis

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	HUANG Qi
	ZHAI Haicheng

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HUANG Qi,ZHAI Haicheng. Impact of Trigonelline on OGD/R-Induced Neuronal Apoptosis Mediated by Mitophagy via Pink1/Parkin Signaling Pathway[J]. HeBei Med, 2023, 29(5): 716-721.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.05.03 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I5/716

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