C肽在1型糖尿病周围神经病变中的保护机制和临床前景

The protective mechanism and clinical prospects of C-peptide in peripheral neuropathy in type 1 diabetes mellitus

摘要

C肽是胰岛素原裂解的副产物，近年研究发现其在1型糖尿病周围神经病变中具有多效保护作用。根据目前的研究，通过激活一氧化氮合酶、Na⁺/K⁺-ATP酶、抑制核因子κB通路等生理机制，C肽不仅能改善神经血流、减轻轴突损伤，还具有抗氧化和抗凋亡作用；除分子水平机制外，动物实验表明，C肽能显著改善1型糖尿病大鼠的神经传导速度、神经周围血流量和结构异常；同时临床试验也表明，C肽替代疗法可以改善1型糖尿病患者的神经传导速度和振动感觉，长效制剂Peg-C肽在1型糖尿病周围神经病变中具有良好应用前景。综上，C肽在1型糖尿病周围神经病变中具备潜在保护作用和临床应用前景。尽管目前已证实C肽可以有效改善神经功能，但其改善神经性疼痛的机制尚未明确。此外，C肽针对神经性疼痛症状的疗效、给药剂量与用药疗程均有待进一步研究明确。

Abstract

Objective: The C-peptide is a by-product of proinsulin cleavage with recently identified probable pleiotropic protective effects in type 1 diabetic peripheral neuropathy（DPN）. Up to now，through its physiological mechanisms like activating nitric oxide synthase，Na⁺/K⁺-ATPase and inhibiting nuclear factor kappa-B pathway，C-peptide can not only improve nerve blood flow and alleviate axonal injury，but also have antioxidant and anti-apoptotic effects. Apart from the molecular mechanism level，animal experiments showed that C-peptide could significantly improve nerve conduction velocity，blood flow and structural abnormalities in diabetic rats. Clinical trials have also shown that C-peptide replacement therapy improves nerve conduction velocity and vibration sensation in patients，and the long-acting formulation Peg-C peptide has more promise. Therefore，C-peptide may have a potential protective effect and clinical application prospect in type 1 DPN. Although it has been proven that C-peptide has an effective role in improving neurological function，its mechanism in the treatment of neuropathic pain has not yet been specifically elucidated. Furthermore，its effect on neuropathic pain symptoms，optimal dosing regimen，and effect on intraepidermal nerve fiber density（IENFD）still need further study.

关键词

C肽 / 周围神经病变 / 1型糖尿病

Key words

C-peptide / peripheral neuropathy / type 1 diabetes

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基金资助

伊犁与江苏省联合卫生研究院江苏省联合项目(yl2022ms02)

江苏省中医药科技发展计划项目(MS2025117)