中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (1): 185-192.doi: 10.12307/2025.002

• 干细胞综述 stem cell review • 上一篇    下一篇

中药调控成骨细胞铁死亡治疗激素性股骨头坏死

张绵钰1,韩  杰2,曾  浩1,陈相汕1,高振罡1   

  1. 1广西中医药大学研究生学院,广西壮族自治区南宁市   530000;2广西中医药大学附属瑞康医院,广西壮族自治区南宁市   530011
  • 收稿日期:2023-11-07 接受日期:2023-12-28 出版日期:2025-01-08 发布日期:2024-05-20
  • 通讯作者: 韩杰,硕士,主任中医师,广西中医药大学附属瑞康医院,广西壮族自治区南宁市 530011
  • 作者简介:张绵钰,男,1999年生,广东省汕头市人,汉族,广西中医药大学在读硕士,主要从事脊柱、骨关节创伤性疾病的中医防治工作。
  • 基金资助:
    国家自然科学基金项目(82260858),项目负责人:韩杰;广西教育厅青年教师科研能力提升项目 (2021KY0290);广西中医药大学高层次人才队伍建设三年行动计划项目:“国医大师韦贵康学术思想与临床诊疗传承发展研究中心”建设项目(2022V001);2022 年广西青年岐黄学者培养项目(桂中医药科教发[2022]13号),项目负责人:韩杰

Regulating ferroptosis of osteoblasts by traditional Chinese medicine in treatment of steroid-induced avascular necrosis of femoral head

Zhang Mianyu1, Han Jie2, Zeng Hao1, Chen Xiangshan1, Gao Zhengang1   

  1. 1Graduate College, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; 2Ruikang Hospital, Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
  • Received:2023-11-07 Accepted:2023-12-28 Online:2025-01-08 Published:2024-05-20
  • Contact: Han Jie, Master, Chief physician, Ruikang Hospital, Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
  • About author:Zhang Mianyu, Master candidate, Graduate College, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China, No. 82260858 (to HJ); Guangxi Education Department Youth Teacher Research Ability Enhancement Project, No. 2021KY0290; Three-Year Action Plan for Construction of High-Level Talent Team at Guangxi University of Chinese Medicine: Construction Project of Research Center for Academic Thought and Clinical Diagnosis and Treatment Inheritance and Development of Chinese Medicine Master Wei Guikang, No. 2022V001; Training Project for Young Qihuang Scholars in Guangxi in 2022, No. [2022]13 (to HJ)

摘要:

文题释义:
铁死亡:是2012年首次提出的一种新型细胞死亡模式,不同于细胞凋亡、细胞坏死和细胞自噬,具有铁的依赖性。其形态特征在于线粒体膜密度的增加和线粒体的收缩,表现为线粒体体积减小,线粒体膜密度增加,线粒体外膜完整性被破坏,线粒体嵴溶解消失。铁死亡发生的主要机制包括细胞内铁超载和活性氧的大量堆积。 
激素性股骨头坏死:是股骨头坏死中的非创伤性一类,是由于糖皮质激素的长期使用导致的股骨头局部血运不良,从而引起骨细胞进一步缺血、坏死、骨小梁断裂、股骨头塌陷的一种病变。其主要病理改变与骨细胞死亡相关,常引起髋关节的疼痛不适和活动障碍。


背景:有研究发现成骨细胞铁死亡可作为重要的发病机制诱导激素性股骨头坏死的发生与发展。随着祖国医学的发展,有学者发现某些中药单体、中药复方及中成药等可通过多种通路机制调控成骨细胞铁死亡,最终起到治疗激素性股骨头坏死的作用。 
目的:探讨成骨细胞铁死亡与激素性股骨头坏死的关系及中草药调控成骨细胞铁死亡治疗激素性股骨头坏死的作用机制,为激素性股骨头坏死的诊治提供新的思路。 
方法:以“铁死亡,激素性股骨头坏死,成骨细胞,中草药,糖皮质激素,铁代谢,活性氧,谷胱甘肽过氧化物酶”为中文检索词,以“ferroptosis,Hormonal necrosis of the femoral head,osteoblast,Chinese herbal medicine,glucocorticoid,iron metabolism,ROS,GPX4”为英文检索词,检索中国知网、PubMed、万方及维普数据库,筛选各数据库建库至2023年成骨细胞铁死亡与激素性股骨头坏死及中草药干预调控研究相关的文章,最终纳入74篇文献进行综述分析。 
结果与结论:①成骨细胞铁死亡在激素性股骨头坏死发病中起重要作用。②成骨细胞铁死亡的发生受到多种机制通路调控,如细胞内铁超载引起铁死亡;细胞发生脂质过氧化损伤细胞膜引起铁死亡;细胞膜上胱氨酸/谷氨酸逆向转运蛋白通过影响谷胱甘肽水平和谷胱甘肽过氧化物酶4活性,从而诱导铁死亡;细胞内发生芬顿反应产生大量活性氧引起铁死亡等。③中药单体淫羊藿苷等、中药复方青娥丸等及中成药补肾活血颗粒等均可通过调控成骨细胞铁死亡的发生,有助于防治激素性股骨头坏死。④目前关于成骨细胞铁死亡相关机制尚不明确,继续深入探明两者的作用机制,有望为临床治疗激素性股骨头坏死提供新选择。

https://orcid.org/0009-0002-3446-2708 (张绵钰);https://orcid.org/0000-0003-1750-4400 (韩杰) 



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: 股骨头坏死, 铁死亡, 中医药, 成骨细胞, 糖皮质激素, 铁代谢, 活性氧, 谷胱甘肽, 谷胱甘肽过氧化物酶, 脂质过氧化

Abstract: BACKGROUND: Some studies have found that ferroptosis of osteoblasts can be an important mechanism to induce the occurrence and development of hormone-induced femoral head necrosis. With the development of Chinese medicine, some scholars have found that some Chinese medicine monomer, Chinese medicine compound and Chinese patent medicine can regulate the ferroptosis of osteoblasts through various pathway mechanisms, and finally play a role in the treatment of steroid-induced avascular necrosis of femoral head.  
OBJECTIVE: To investigate the relationship between ferroptosis and steroid-induced avascular necrosis of femoral head and the mechanism of Chinese medicine regulating ferroptosis of osteoblasts in the treatment of steroid-induced avascular necrosis of femoral head, so as to provide new ideas for the diagnosis and treatment of steroid-induced avascular necrosis of femoral head. 
METHODS: With “ferroptosis, steroid-induced avascular necrosis of femoral head, osteoblast, Chinese herbal medicine, glucocorticoid, iron metabolism, reactive oxygen species, glutathione peroxidase” as Chinese search terms, and “ferroptosis, hormonal necrosis of the femoral head, osteoblast, Chinese herbal medicine, glucocorticoid, iron metabolism, ROS, GPX4” as English search terms, the search was conducted on CNKI, PubMed, WanFang, VIP and other databases. The relevant articles on osteoblast ferroptosis and steroid-induced avascular necrosis of femoral head and the regulation of Chinese herbal medicine intervention from the establishment of each database to 2023 were screened. Finally, 76 articles were systematically analyzed. 
RESULTS AND CONCLUSION: (1) Ferroptosis of osteoblasts plays an important role in the pathogenesis of steroid-induced avascular necrosis of femoral head. (2) The occurrence of ferroptosis in osteoblasts is regulated by a variety of mechanisms, such as intracellular iron overload causing ferroptosis. Lipid peroxidation damages cell membrane and causes ferroptosis. Cystine/glutamate reverse transporter induced ferroptosis by influencing glutathione level and glutathione peroxidase 4 activity. Fenton reaction in the cell produces a large number of reactive oxygen species and causes ferroptosis. (3) Chinese medicine monomer icariin, Chinese medicine compound Qinge pills and Chinese patent medicine Bushen Huoxue granules can regulate the occurrence of osteoblast ferroptosis, and help to prevent and treat steroid-induced avascular necrosis of femoral head. (4) The mechanism of ferroptosis in osteoblasts is still unclear. Further investigation on the mechanism of action of both is expected to provide a new choice for clinical treatment of steroid-induced avascular necrosis of femoral head.  

Key words: avascular necrosis of femoral head, ferroptosis, traditional Chinese medicine, osteoblast, glucocorticoid, iron metabolism, reactive oxygen species, glutathione, glutathione peroxidase, lipid peroxidation

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