肾上腺髓质素及其受体在糖尿病周围神经病变中的作用机制

doi:10.12092/j.issn.1009-2501.2026.08.015

摘要/Abstract

摘要：

糖尿病周围神经病变（diabetic peripheral neuropathy，DPN）是糖尿病最具致残性的慢性并发症之一，其病理机制涉及ir、氧化应激、炎症反应及神经损伤等多重因素。肾上腺髓质素（adrenomedullin，AM）作为一种具有广泛生物学活性的肽类分子，通过与其受体降钙素受体样受体/受体活性修饰蛋白结合，在DPN的发生发展中呈现复杂调控作用。本文系统探讨了AM及其受体通过调控ir、内皮功能障碍、脂质代谢紊乱、氧化应激及炎症反应等多重机制参与DPN的病理进程。然而，AM在不同生理及病理阶段具有双向调节特性，其积极效应与消极效应共存的现象可能源于多重机制的交织与调控差异。本文系统总结了AM及其受体在DPN中的分子机制及治疗潜力，探讨其作为多靶点治疗策略的可能性，为靶向AM信号通路的精准干预提供理论依据。

关键词: 肾上腺髓质素, 糖尿病周围神经病变, ir, 肥胖

Abstract:

Diabetic Peripheral Neuropathy (DPN) is one of the most disabling chronic complications of diabetes mellitus, and its pathogenesis involves multiple factors such as insulin resistance, oxidative stress, inflammatory response, and neurological injury. Adrenomedullin (AM), as a peptide molecule with a wide range of biological activities, exhibits a complex regulatory role in the development of DPN by binding to its receptors CRLR/RAMPs. In this paper, we systematically reviewed the involvement of AM and its receptor in the pathological process of DPN through multiple mechanisms, such as the regulation of insulin resistance, endothelial dysfunction, lipid metabolism disorders, oxidative stress and inflammatory response. However, the bidirectional regulatory properties of AM at different physiological and pathological stages, and the coexistence of its positive and negative effects may stem from the intertwining of multiple mechanisms and regulatory differences. In this paper, we systematically summarize the molecular mechanisms and therapeutic potential of AM and its receptors in DPN, reveal its potential as a multi-target therapeutic strategy, and provide an important theoretical basis for future precision interventions targeting the AM signaling pathway.

Key words: adrenomedullin, diabetic peripheral neuropathy, insulin resistance, obesity

中图分类号:

卢爱琳, 吴永青, 袁梦蕊, 刘弘毅. 肾上腺髓质素及其受体在糖尿病周围神经病变中的作用机制[J]. 中国临床药理学与治疗学, 2026, 31(8): 1144-1152.

Ailin LU, Yongqing WU, Mengrui YUAN, Hongyi LIU. Mechanism of action of adrenomedullin and its receptors in diabetic peripheral neuropathy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(8): 1144-1152.

图/表 4

图 1 不同的实验条件下AM对胰岛素分泌的影响

Fig.1 Effect of AM on insulin secretion under different experimental conditions

图 2 肥胖相关DPN中AM诱导的内皮ir机制

Fig.2 Mechanism of AM-induced endothelial insulin resistance in obesity-related DPN

图 3 AM在DPN中参与神经病理性疼痛的机制

Fig.3 Mechanisms of AM involvement in neuropathic pain in the DPN

图 4 AM在DPN中的潜在应用概要图

Fig.4 Summary diagram of potential applications of AM in DPN

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