中医药基于自噬防治糖尿病周围神经病变的实验研究进展

Experimental research progress in traditional Chinese medicine prevention and treatment of diabetic peripheral neuropathy based on autophagy

糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)是糖尿病发展至后期导致周围神经损伤的慢性并发症,存在氧化应激、内质网应激、神经炎症、雪旺细胞(Schwann cells,SCs)凋亡等多种病理变化,是导致糖尿病患者下肢残疾或截肢的主要因素,发病率较高,病程长且预后差。目前,现代医学对DPN的治疗以控制血糖、改善微循环及营养神经为主,但仅能改善患者的临床症状,不能从根本上逆转周围神经的病理改变。自噬是一种自我清除机制,通过清除多余的代谢物从而维持细胞内稳态。中医药(traditional Chinese medicine,TCM)结合中医理论,从整体观念和辨证论治的角度出发,具有多靶点、多通路、范围广的特点,在治疗慢性疾病中发挥重要作用。现代研究表明,DPN的发生发展与多种病理改变相关,而自噬是近几年发现的与DPN密切相关的机制之一,持续的高糖环境使得周围神经细胞自噬被抑制或过度激活,造成神经细胞的不可逆损伤,从而参与DPN发生发展的全过程。因此,恢复自噬平衡,减轻神经损伤是治疗DPN的关键途径之一。近几年,部分研究已经证实一些中药活性成分及复方可以通过调控自噬通路,抑制DPN氧化应激反应的发生、内质网应激的激活、线粒体损伤、炎症反应的发生及SCs的凋亡,从而发挥防治DPN的作用,但目前缺乏对该领域的系统性整理和归纳。基于此,该文梳理了国内外文献,分析阐释中医药通过调控自噬防治DPN的作用机制,探讨中医药干预自噬治疗DPN的潜在靶点,以期为临床研究与药物开发提供新思路。

Diabetic peripheral neuropathy(DPN)is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes.It involves a variety of pathological changes such as oxidative stress,endoplasmic reticulum stress,neuroinflammation,and apoptosis of Schwann cells(SCs).DPN is the main factor leading to lower limb disability or amputation in diabetic patients,with high incidence,long disease course,and poor prognosis.The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition,which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves.Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites.Traditional Chinese medicine(TCM),featuring the holistic concept and syndrome differentiation,can treat chronic diseases in a multi-target,multi-pathway,and wide-range manner.Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes,and autophagy is a key mechanism associated with DPN.The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells,which causes irreversible damage of nerve cells and the occurrence and development of DPN.Therefore,restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN.The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress,endoplasmic reticulum stress,mitochondrial damage,inflammation,and apoptosis of SCs in DPN by regulating the autophagy pathway,thus playing a role in the prevention and treatment of DPN.However,the systematic induction in this field remains to be carried out.This paper reviewed the relevant literature,explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy,and summarized the potential targets of TCM in the treatment of DPN,with a view to providing new ideas for clinical research and drug development.