| 路 瑶,杨晶晶,万尖尖,马雪莲,赵子暄.利拉鲁肽改善SH-SY5Y细胞氧化应激、线粒体功能障碍、自噬损伤的机制研究[J].,2024,(23):4408-4413 |
| 利拉鲁肽改善SH-SY5Y细胞氧化应激、线粒体功能障碍、自噬损伤的机制研究 |
| Mechanism of Liraglutide Improving Oxidative Stress, Mitochondrial Dysfunction and Autophagy Damage in SH-SY5Y Cells |
| 投稿时间：2024-06-18 修订日期：2024-07-10 |
| DOI：10.13241/j.cnki.pmb.2024.23.002 |
| 中文关键词: 利拉鲁肽 神经母细胞瘤 氧化应激 线粒体功能 自噬 |
| 英文关键词: Liraglutide Human neuroblastoma Oxidative stress Mitochondrial dysfunction Autophagy |
| 基金项目:省部共建中亚高发病成因与防治国家重点实验室代谢病专项基金项目（SKL-HIDCA-2022-DX6）；新疆维吾尔自治区自然科学基金项目（2020D01C183） |
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| 中文摘要: |
| 摘要 目的：探讨利拉鲁肽（Lira）干预人神经母细胞瘤（SH-SY5Y）细胞对氧化应激、线粒体功能及自噬损伤的机制。方法：将SH-SY5Y细胞分为对照组、高糖（HG）组、HG+LI-L组、HG+LI-H组、HG+LI-H+3-甲基腺嘌呤（3MA）组。检测细胞增殖能力、Glu、丙二醛（MDA）、三磷酸腺苷（ATP）和超氧化物歧化酶（SOD）水平、细胞凋亡、活性氧（ROS）水平和线粒体膜电位、微管相关蛋白1轻链3（LC3B）和p62蛋白表达及定位、磷脂酰肌醇3激酶（PI3K）、p-PI3K、哺乳动物雷帕霉素靶蛋白（mTOR）、p-mTOR、蛋白激酶B（Akt）、p-Akt蛋白表达。结果：与HG组比较，HG+LI（500 nM）组细胞增殖活力最为显著，HG+LI（500 nM）组Glu和MDA降低，SOD升高，HG+LI-L组和HG+LI-H组细胞存活率、ATP和SOD升高，细胞凋亡率、ROS荧光强度、Glu、MDA和JC-1下降，且HG+LI-H组细胞存活率、ATP和SOD高于HG+LI-L组，细胞凋亡率、ROS荧光强度、Glu、MDA、JC-1低于HG+LI-L组，HG+LI-H组p-mTOR和p62蛋白表达降低，p-PI3K、p-Akt和LC3B蛋白表达升高（P<0.05）。与对照组比较，HG组Glu、MDA、细胞凋亡率、细胞ROS荧光强度、Glu、MDA、JC-1、p-mTOR、p62蛋白表达升高，SOD、ATP、细胞存活率、p-PI3K、p-Akt和LC3B蛋白表达降低（P<0.05）。与HG+LI-H组比较，HG+LI-H+3MA组细胞存活率、ATP、SOD、p-PI3K、p-Akt和LC3B蛋白表达下降，细胞凋亡率、ROS荧光强度、Glu、MDA、JC-1、p-mTOR、p62蛋白表达升高（P<0.05）。结论：Lira可能是以剂量依赖的方式降低SH-SY5Y细胞内氧化应激，改善线粒体功能和PI3K/AKT/mTOR自噬通路，发挥抗凋亡和保护神经细胞作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the mechanism of liraglutide (Lira) intervention on oxidative stress, mitochondrial function and autophagy damage in human neuroblastoma (SH-SY5Y) cells. Methods: SH-SY5Y cells were divided into control group, high glucose (HG) group, HG+LI-L group, HG+LI-H group HG+LI-H+3-methyladenine (3MA) group. The cell proliferation ability, the levels of Glu, malondialdehyde (MDA), adenosine triphosphate (ATP), superoxide dismutase (SOD), Cell apoptosis, reactive oxygen species (ROS) level, mitochondrial membrane potential. The expression and localization of microtubule-associated protein 1 light chain 3 (LC3B), p62, The expression of phosphatidylinositol 3-kinase (PI3K), p-PI3K, mammalian rapamycin target protein (mTOR) p-mTOR , protein kinase B (Akt) and p-Akt protein were detected. Results: Compared with HG group, the cell proliferation activity in HG+LI (500 nM) group was the most significant, Glu and MDA decreased and SOD increased in HG+LI (500 nM) group, the cell viability, ATP and SOD were increased, and the apoptosis rate, ROS fluorescence intensity, Glu, MDA and JC-1 were decreased in HG+LI-L group and HG+LI-H group, and the cell viability, ATP and SOD in HG+LI-H group were higher than those in HG+LI-L group, and the apoptosis rate, ROS fluorescence intensity, Glu, MDA and JC-1 were lower than those in HG+LI-L group, p-mTOR and p62 proteins expression were decreased, p-PI3K, p-Akt and LC3B proteins expression were increased in the HG+LI-H group (P<0.05). Compared with control group, Glu, MDA, apoptosis rate, ROS fluorescence intensity, Glu, MDA, JC-1, P-mTOR and p62 protein expression in HG group increased, while SOD, ATP, cell survival rate, p-PI3K, p-Akt and LC3B protein expression decreased (P<0.05). Compared with HG+LI-H group, the cell viability, ATP, SOD, p-PI3K, p-Akt and LC3B protein expression were decreased, and the apoptosis rate, ROS fluorescence intensity, Glu, MDA JC-1, p-mTOR and p62 protein expression were increased in HG+LI-H+3MA group (P<0.05). Conclusion: Lira may reduce oxidative stress in SH-SY5Y cells in a dose-dependent manner, improve mitochondrial function and PI3K/AKT/mTOR autophagy pathway, Play a role in resist apoptosis and protect nerve cells. |
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