药学学报, 2018, 53(4): 546-552
引用本文:
张钊, 王莎莎, 朱天碧, 楚世峰, 陈乃宏. 人参皂苷Rg1调控miR-153/Nrf2/HO-1减轻肌萎缩侧索硬化模型小鼠损伤[J]. 药学学报, 2018, 53(4): 546-552.
ZHANG Zhao, WANG Sha-sha, ZHU Tian-bi, CHU Shi-feng, CHEN Nai-hong. Rg1 alleviates the damage in ALS model through regulation of miR153/Nrf2/HO-1[J]. Acta Pharmaceutica Sinica, 2018, 53(4): 546-552.

人参皂苷Rg1调控miR-153/Nrf2/HO-1减轻肌萎缩侧索硬化模型小鼠损伤
张钊1, 王莎莎1,2, 朱天碧1,3, 楚世峰1, 陈乃宏1,2,3
1. 中国医学科学院药物研究所神经科学中心, 天然药物活性物质与功能国家重点实验室, 北京 100050;
2. 山西中医药大学中药学院, 山西 太原 030619;
3. 湖南中医药大学药学院, 湖南 长沙 410208
摘要:
本文主要通过肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)模型小鼠(SOD1 G93A)研究人参皂苷Rg1对ALS病程及病理的影响,并对其作用机制进行分析。通过体重及生存率监测小鼠病程,转棒实验测试小鼠肌肉运动协调能力,甲苯胺蓝染色及免疫荧光检测小鼠脊髓运动神经元及小胶质细胞改变,Western blot检测氧化应激相关蛋白Nrf2等的表达,并对其及相关miRNA进行干预,验证Rg1的作用及相关机制。结果显示20 mg·kg-1·d-1 Rg1可明显延缓ALS小鼠病程,改善其运动症状,减少脊髓运动神经元丢失并抑制小胶质细胞激活。进一步研究发现Rg1通过抑制ALS小鼠脊髓miR-153表达,解除其对Nrf2转录后抑制,使其表达明显上调,进而激活HO-1抗氧化信号通路。本研究表明Rg1通过调节miR-153/Nrf2/HO-1抗氧化损伤,对ALS小鼠发挥神经保护作用,为将Rg1开发为有效的ALS治疗药物提供理论依据。
关键词:    肌萎缩侧索硬化症      人参皂苷Rg1      氧化应激损伤      NF-E2-相关因子2      miR-153     
Rg1 alleviates the damage in ALS model through regulation of miR153/Nrf2/HO-1
ZHANG Zhao1, WANG Sha-sha1,2, ZHU Tian-bi1,3, CHU Shi-feng1, CHEN Nai-hong1,2,3
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicine, Neuroscience Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China;
2. College of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China;
3. College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
Abstract:
The impact of Rg1 in the disease progress and pathology of amyotrophic lateral sclerosis (ALS) was investigated in mouse model (SOD1 G93A). Body weight and survival rate were monitored to check the course of disease. Rotarod test was used to evaluate the coordination of muscle movement. Toluidine blue staining and immunofluorescence were used to check the effect of Rg1 on motor neuron and microglia. The expression of oxidative stress related protein Nrf2 and the miRNA were tested to investigate the mechanism of Rg1. We found that 20 mg·kg-1·d-1 Rg1 significantly postponed the disease onset and process, improved the motor syndrome, reduced the loss of motor neuron and inhibited the activation of microglia cells. Rg1 inhibited the aggregation of miR-153 in the spinal cord of ALS mice, which relieved the inhibition of Nrf2 and contributed to its up-regulation in the activation of HO-1 anti-oxidative signal pathway. Our study confirmed that Rg1 could protect ALS mice from oxidative damage through the up-regulation of miR-153/Nrf2/HO-1, which provides a theoretical foundation for Rg1 application to the ALS treatment.
Key words:    amyotrophic lateral sclerosis    ginsenoside Rg1    oxidative stress damage    NF-E2-related factor 2    miR-153   
收稿日期: 2017-10-16
DOI: 10.16438/j.0513-4870.2017-1012
基金项目: 国家自然科学基金资助项目(81603316,81603315);2017年湖南省中药饮片标准化及功能工程技术研究中心开放基金资助项目(BG201701);中国医学科学院医学与健康科技创新工程经费资助(2016-I2M-1-004).
通讯作者: 陈乃宏,Tel/Fax:86-10-63165177,E-mail:chennh@imm.ac.cn
Email: chennh@imm.ac.cn
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