基于阴阳理论探讨中医药干预铁死亡的研究进展

Traditional Chinese Medicine Intervention of Ferroptosis Based on Yin-yang Theory:A Review

铁死亡是一种铁依赖性的新型细胞程序性死亡方式,与谷胱甘肽/谷胱甘肽过氧化物酶4、铁代谢、脂代谢、铁自噬等多条途径有关,并参与多个疾病的病理过程,如肿瘤、脑缺血、帕金森等。铁死亡具有双向调节作用,诱导铁死亡可以促进病理状态细胞的消除(如肿瘤细胞),但长期诱导铁死亡又可能会导致或加重其他脂质代谢异常和铁代谢异常相关疾病,调节细胞增殖与铁死亡之间的平衡可能成为药物干预疾病的重要靶点。阴阳学说贯穿中医学理论体系始终,被用来说明人体的生理功能和病理变化,并指导疾病的诊断、防治以及养生保健。细胞增殖与程序性死亡的平衡实质上是阴阳在细胞水平上的平衡,受平衡规律的支配与调控。中医药干预铁死亡主要体现在促进肿瘤细胞铁死亡(损其有余)和抑制其他疾病铁死亡(补其不足)2个方面,与调整阴阳的治则治法有异曲同工之妙。基于此,该文拟通过阴阳理论来阐明中医药促进铁死亡和抑制铁死亡的关系,以期为阴阳学说的现代应用提供依据,为中医药治疗提供新靶点。

Ferroptosis,a new type of iron-dependent programmed cell death,is related to multiple pathways such as glutathione/glutathione peroxidase 4,iron metabolism,lipid metabolism,and iron autophagy,and plays an important part in the occurrence and development of many diseases,such as tumor,cerebral ischemia,and Parkinson’s disease.Ferroptosis is a double-edged sword as it can eliminate pathological cells(such as tumor cells)but long-term ferroptosis may cause or aggravate other disorders related to abnormal lipid metabolism and iron metabolism.Regulating the balance between cell proliferation and ferroptosis may be an important target for drug intervention in diseases.The Yin-yang theory is one of the foundational principles of traditional Chinese medicine(TCM),which is used to explain the physiological functions and pathological changes of human body and to guide the diagnosis and prevention of disease and health care.The balance of cell proliferation and programmed death is essentially the balance of Yin and Yang at the cellular level,which is governed and regulated by the law of balance.TCM intervenes in ferroptosis by promoting ferroptosis of tumor cells(damaging the excess)and inhibiting ferroptosis of other diseases(compensating the deficiency),which is similar to the treatment principle of adjusting Yin and Yang.On this basis,this article aims to use the Yin-yang theory to clarify the relationship between TCM promoting ferroptosis and inhibiting ferroptosis,which is expected to lay a basis for the modern application of Yin-yang theory and provide new targets for TCM treatment.