Feng Hao-Yue, Ding Rui, Zhou Qi, Wu Ting-Chao, Li Hui, Ma Xi-Tao, Yue Ren-Song
Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610072, China.
Department of Ophthalmology, the Affiliated Hospital of Southwest Medical University Luzhou 646000, China.
Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(2):300-310. doi: 10.19540/j.cnki.cjcmm.20220905.707.
As one of the most frequent complications of diabetes, diabetic neuropathy often involves peripheral and central nervous systems. Neuroinflammation is the key pathogenic factor of secondary nerve injury in diabetes. NOD-like receptor pyrin domain-containing 3(NLRP3) inflammasome is a group of subcellular multiprotein complexes, including NLRP3, apoptosis associated speck-like protein(ASC), and pro-cysteinyl aspartate specific proteinase 1(pro-caspase-1). NLRP3 inflammasome is an inducer of innate immune responses. Its activation stimulates the inflammatory cascade reaction, promotes the release of inflammatory mediators, triggers cell death and uncontrolled autophagy, activates glial cells, facilitates peripheral immune cell infiltration, and initiates amyoid β(Aβ)-tau cascade reactions. As a result, it contributes to the central nerve, somatic nerve, autonomic nerve, and retinal nerve cell damage secondary to diabetes. Therefore, due to its key role in the neuroinflammation responses of the body, NLRP3 inflammasome may provide new targets for the treatment of diabetic neuropathy. With multi-target and low-toxicity advantages, traditional Chinese medicine plays a vital role in the treatment of diabetic neuropathy. Accumulating evidence has shown that traditional Chinese medicine exerts curative effects on diabetic neuropathy possibly through regulating NLRP3 inflammasome. Although the role of NLRP3 inflammasome in diabetes and related complications has been investigated in the literature, systematical studies on drugs and mechanism analysis for secondary neuropathy are still lacking. In this article, the role of NLRP3 inflammasome in diabetic neuropathy was explored, and the research progress on traditional Chinese medicine in the treatment of diabetic neuropathy through NLRP3 inflammasome was reviewed.
作为糖尿病最常见的并发症之一,糖尿病性神经病变常累及周围神经系统和中枢神经系统。神经炎症是糖尿病继发性神经损伤的关键致病因素。含NOD样受体吡咯结构域蛋白3(NLRP3)炎性小体是一组亚细胞多蛋白复合物,包括NLRP3、凋亡相关斑点样蛋白(ASC)和半胱天冬酶原-1(pro-caspase-1)。NLRP3炎性小体是先天性免疫反应的诱导剂。其激活可刺激炎症级联反应,促进炎症介质的释放,引发细胞死亡和失控的自噬,激活神经胶质细胞,促进外周免疫细胞浸润,并启动淀粉样β(Aβ)-tau级联反应。因此,它会导致糖尿病继发的中枢神经、躯体神经、自主神经和视网膜神经细胞损伤。因此,由于其在机体神经炎症反应中的关键作用,NLRP3炎性小体可能为糖尿病性神经病变的治疗提供新靶点。中药具有多靶点、低毒性的优势,在糖尿病性神经病变的治疗中发挥着重要作用。越来越多的证据表明,中药可能通过调节NLRP3炎性小体对糖尿病性神经病变发挥治疗作用。尽管已有文献对NLRP3炎性小体在糖尿病及其相关并发症中的作用进行了研究,但针对继发性神经病变的药物及作用机制分析仍缺乏系统研究。本文探讨了NLRP3炎性小体在糖尿病性神经病变中的作用,并综述了中药通过NLRP3炎性小体治疗糖尿病性神经病变的研究进展。