中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (25): 4087-4093.doi: 10.12307/2024.146

• 干细胞综述 stem cell review • 上一篇    下一篇

中药及间充质干细胞调控免疫反应治疗肌萎缩侧索硬化症的作用机制

王绍娜1,高  晨1,樊飞燕1,刘飞祥2,张运克1,2   

  1. 1河南中医药大学,河南省郑州市   450046;2河南中医药大学第一附属医院,河南省郑州市   450046
  • 收稿日期:2023-03-08 接受日期:2023-04-24 出版日期:2024-09-08 发布日期:2023-11-24
  • 通讯作者: 张运克,二级主任医师,博士,教授,博士生导师,博士后合作导师,河南中医药大学,河南省郑州市 450046;河南中医药大学第一附属医院,河南省郑州市 450000
  • 作者简介:王绍娜,女,1996年生,河南省郑州市人,汉族,河南中医药大学在读硕士,主要从事中医药防治脑血管疾病的研究。
  • 基金资助:
    国家自然科学基金(81974564),项目负责人:张运克;国家自然科学基金(82104730),项目负责人:刘飞祥;中原英才计划—科技创新领军人才(224200510027),项目负责人:张运克

Action mechanism of traditional Chinese medicine and mesenchymal stem cells regulating immune response in treatment of amyotrophic lateral sclerosis

Wang Shaona1, Gao Chen1, Fan Feiyan1, Liu Feixiang2, Zhang Yunke1, 2   

  1. 1Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China; 2The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
  • Received:2023-03-08 Accepted:2023-04-24 Online:2024-09-08 Published:2023-11-24
  • Contact: Zhang Yunke, Chief physician, MD, Professor, Doctoral supervisor, Post-doctoral cooperative supervisor, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China; The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
  • About author:Wang Shaona, Master candidate, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 81974564 (to ZYK); National Natural Science Foundation of China, No. 82104730 (to LFX); Central Plains Talent Program - Leading Talents in Science and Technology Innovation, No. 224200510027 (to ZYK)

摘要:


文题释义:

间充质干细胞:是一种容易从不同体细胞分离出的成体细胞,同其他干细胞相比,具有易于扩增、无免疫排斥和低伦理争论等特点,且能发挥免疫调节作用保护运动神经元回路进而显著改善受损大脑区域的微环境,成为治疗神经退行性疾病的有力候选细胞。
肌萎缩侧索硬化:是进行性上下运动神经元变性的神经退行性疾病,其发病机制复杂、有效治疗手段少、死亡率高,可引发运动及运动外症状。


背景:肌萎缩侧索硬化为一种进行性神经退行性疾病,常导致大脑和脊髓神经元死亡。肌萎缩侧索硬化发病机制极为复杂,难治率、死亡率高且目前其治疗药物仅有2种,因此开发新治疗方法以改善患者预后迫在眉睫。

目的:综述中药及间充质干细胞调控免疫反应治疗肌萎缩侧索硬化的作用机制。
方法:以“traditional Chinese medicine,mesenchymal stem cells,ALS,immune response” 为英文检索词,以“中药,间充质干细胞,肌萎缩侧索硬化,免疫反应”为中文检索词,检索万方、中国知网、PubMed及Web of Science数据库 2010-2023年的相关文献,最终纳入69篇文献进行综述分析。

结果与结论:①中药调控免疫反应治疗肌萎缩侧索硬化可总结为5个机制:主要包括冰片和黄芪甲苷等中药促进闭锁小带蛋白1、闭合蛋白5表达重建血液中枢神经系统屏障完整性;复方扶芳藤合剂调节自然杀伤细胞表面受体分子抑制其自身毒性;半枝莲和广藿香等作用补体系统因子抑制其异常激活;雷公藤和钩藤等介导细胞外信号调节激酶1/2衰减诱导型一氧化氮合酶产生而抑制小胶质细胞活化;左归丸、栝蒌根等促进白细胞介素10表达调控T细胞改善免疫环境。②通过现有研究总结了间充质干细胞调控免疫反应治疗肌萎缩侧索硬化可总结为5个机制:减少水通道蛋白4表达和降低内皮型一氧化氮合酶信号传导等方面修复免疫屏障完整性;释放吲哚胺2,3-双加氧酶和前列腺素E2等因子抗自然杀伤细胞毒性;分泌因子H干扰转化酶活性抑制补体系统异常激活;调控CX3CL1/CX3CR1系统轴或分泌转化生长因子β等途径改变小胶质细胞表型抑制其活性;增加白细胞介素10表达或激活STATS磷酸化通路来恢复T细胞功能。③目前中药联合间充质干细胞治疗肌萎缩侧索硬化研究较少,已知的相关研究报道显示,肌萎灵注射液可促进干细胞增殖分化以及补阳还五汤联合骨髓间充质干细胞显著提高血脑屏障完整性,未来还需进一步探讨两者对难治性肌萎缩侧索硬化的协同治疗效果。

https://orcid.org/0000-0003-1500-1535 (张运克) 

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 肌萎缩侧索硬化, 免疫反应, 中药, 提取物, 复方, 间充质干细胞, 运动神经元, 作用机制, 信号通路, 炎症因子

Abstract: BACKGROUND: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease, which often leads to the death of neurons in the brain and spinal cord. The pathogenesis of amyotrophic lateral sclerosis is extremely complex, with high refractory rate and mortality rate. There are only two kinds of drugs for its treatment, so it is urgent to develop new treatment methods to improve the prognosis of patients.
OBJECTIVE: To review the mechanism of Chinese medicine and mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis. 
METHODS: “Traditional Chinese medicine, medical stem cells, ALS, immune response” were Chinese and English search terms. Articles were retrieved from WanFang, CNKI, PubMed, Web of Science and other databases from 2010 to 2023. Finally, 69 articles were included for review.
RESULTS AND CONCLUSION: (1) The article summarizes in detail the five mechanisms of traditional Chinese medicine regulating the immune response in the treatment of amyotrophic lateral sclerosis: mainly including the promotion of expression of closed zone protein-1 and closed protein-5 by traditional Chinese medicine such as borneol and astragaloside IV to rebuild the integrity of the blood central nervous system barrier. Fufangteng Mixture can regulate the receptor molecules on the surface of the natural killer cells to inhibit their autotoxicity. The complement system factors such as Scutellaria barbata and patchouli can inhibit their abnormal activation. Tripterygium wilfordii and Uncaria rhynchophylla inhibit the activation of microglia by mediating the production of extracellular signal-regulated kinase 1/2 attenuated inducible nitric oxide synthase. Zuogui Pill and Trichosanthes kirilowii Root promote the expression of interleukin-10 and regulate T cells to improve the immune environment. (2) Through existing research, five mechanisms of mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis have been summarized, mainly including reducing the expression of aquaporin 4 and reducing endothelial nitric oxide synthase signal transduction to repair the integrity of the immune barrier; releasing indoleamine 2,3-dioxygenase, prostaglandin E2 and other factors to resist natural killer cell toxicity; secretion factor H interferes with the activity of invertase and inhibits abnormal activation of the complement system; regulating the CX3CL1/CX3CR1 system axis or secreting transforming growth factors β, which can change the phenotype of microglia and inhibit its activity by other ways; increasing the expression of interleukin-10 or activating the STATS phosphorylation pathway to restore T cell function. (3) At present, there are few studies on the combination of traditional Chinese medicine and mesenchymal stem cells in the treatment of amyotrophic lateral sclerosis. Relevant research reports have shown that Jiweiling Injection can promote stem cell proliferation and differentiation and that Buyang Huanwu decoction combined with bone marrow mesenchymal stem cells can significantly improve the integrity of the blood-brain barrier. In the future, further exploration is needed to explore the synergistic treatment effect of both on refractory amyotrophic lateral sclerosis.

Key words: amyotrophic lateral sclerosis, immune response, traditional Chinese medicine, extract, compound formula, mesenchymal stem cell, motor neuron, action mechanism, signaling pathway, inflammatory factor

中图分类号: