金线莲苷对诱导多能干细胞来源的肌萎缩侧索硬化症模型的神经保护作用*

doi:10.3870/j.issn.1672-0741.26.03.018

华中科技大学学报（医学版） ›› 2026, Vol. 55 ›› Issue (4): 457-464.doi: 10.3870/j.issn.1672-0741.26.03.018

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金线莲苷对诱导多能干细胞来源的肌萎缩侧索硬化症模型的神经保护作用^*

黄蕴洁¹, 李香玲¹, 周秋至^1,2, 李雅洁^1,2, 陈红^1,2,3△

华中科技大学同济医学院附属同济医院 ¹康复科 ²干细胞中心,武汉 430030
³华中科技大学湖北省神经损伤与功能重建重点实验室,武汉 430030

收稿日期:2026-03-08 出版日期:2026-08-15 发布日期:2026-07-28
通讯作者: ^△E-mail:chenhong1129@hust.edu.cn
作者简介:黄蕴洁,女,1999年生,硕士研究生,E-mail:M202376557@hust.edu.cn
基金资助:
^*国家自然科学基金资助项目(No.82472621)

Neuroprotective Effects of Kinsenoside in an iPSC-derived ALS Model

Huang Yunjie¹, Li Xiangling¹, Zhou Qiuzhi^1,2, et al

¹Department of Rehabilitation,²Stem Cell Research Center,Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

Received:2026-03-08 Online:2026-08-15 Published:2026-07-28
Contact: ^△E-mail:chenhong1129@hust.edu.cn

摘要/Abstract

摘要： 目的基于诱导多能干细胞(induced pluripotent stem cell,iPSC)衍生的运动神经元细胞模型,探讨金线莲苷对于肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)的治疗作用及潜在机制。方法以携带SOD1^D90A突变的iPSC分化的运动神经元为ALS模型,以经TALEN技术修正为SOD1野生型(SOD1^D90D)的同源运动神经元作为对照。首先确定金线莲苷作用于ALS细胞模型的安全浓度范围及最佳给药浓度;随后通过形态学评估检测其对轴突变性病理表型的改善作用,并测定细胞能量代谢的变化;进一步通过分子生物学技术测定氧化应激通路关键分子KEAP1/Nrf2的表达水平,并探究金线莲苷潜在下游作用靶点。结果在金线莲苷干预的ALS细胞模型中,病理表型得到显著改善,具体表现为轴突肿胀程度减轻、轴突长度增加;同时,肿胀轴突内线粒体异常聚集现象明显缓解,细胞内ATP水平显著升高,培养基上清液中乳酸含量降低。机制研究显示,给药后ALS模型细胞中KEAP1蛋白水平下降,Nrf2蛋白水平上升;qRT-PCR结果显示,金线莲苷能够回调线粒体融合相关基因MFN2、OPA1及线粒体自噬相关基因PINK1的mRNA表达水平。结论金线莲苷可能通过调控KEAP1/Nrf2氧化应激通路,以及线粒体融合与自噬相关基因的表达,改善ALS运动神经元模型的病理损伤。

关键词: 肌萎缩侧索硬化, 运动神经元, 金线莲苷, 药物治疗, 线粒体功能

Abstract: Objective To investigate the therapeutic effects and mechanisms of kinsenoside in amyotrophic lateral sclerosis(ALS)using an induced pluripotent stem cell(iPSC)-derived motor neuron model.Methods Motor neurons differentiated from SOD1^D90A mutant iPSCs were used as the ALS model.Isogenic motor neurons corrected to wild-type SOD1(SOD1^D90D)via TALEN technology served as controls.The safe concentration range and optimal treatment concentration of kinsenoside in the ALS cell model were determined.Morphological assessments were then conducted to evaluate its ameliorative effects on axonal degeneration phenotypes,and changes in cellular energy metabolism were measured.Expression levels of KEAP1/Nrf2,key molecules in the oxidative stress pathway,were determined by molecular biology techniques,and potential downstream targets were investigated.Results In the ALS cell model treated with kinseoside,pathological phenotypes were significantly ameliorated,as evidenced by reduced axonal swelling and increased axonal length.Meanwhile,abnormal mitochondrial aggregation within swollen axons was markedly alleviated,intracellular ATP levels were significantly elevated,and lactate content in the culture supernatant was reduced.Mechanistic studies revealed that after kinseoside treatment,KEAP1 protein levels decreased while Nrf2 protein levels increased in ALS model cells.TheqRT-PCR results confirmed that kinseoside reversed the mRNA transcription levels of mitochondrial fusion-related genes MFN2 and OPA1,as well as the mitophagy-related gene PINK1.Conclusion Kinsenoside may ameliorate the pathological damage of ALS motor neuron model by regulating the KEAP1/Nrf2 oxidative stress pathway and the expression of genes related to mitochondrial fusion and mitophagy.

Key words: amyotrophic lateral sclerosis, motor neuron, kinsenoside, pharmacotherapy, mitochondrial function

中图分类号:

R746.4

黄蕴洁, 李香玲, 周秋至, 李雅洁, 陈红. 金线莲苷对诱导多能干细胞来源的肌萎缩侧索硬化症模型的神经保护作用^*[J]. 华中科技大学学报（医学版）, 2026, 55(4): 457-464.

Huang Yunjie, Li Xiangling, Zhou Qiuzhi, et al. Neuroprotective Effects of Kinsenoside in an iPSC-derived ALS Model[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(4): 457-464.

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金线莲苷对诱导多能干细胞来源的肌萎缩侧索硬化症模型的神经保护作用^*

Neuroprotective Effects of Kinsenoside in an iPSC-derived ALS Model

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