Yu Honghai, Yang Cunqing, Wang Guoqiang, Lv Jiao, Li Xiangyan, Qi Wenxiu, Wang Xiuge
College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China.
Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
Curr Pharm Des. 2025;31(29):2370-2384. doi: 10.2174/0113816128362557250314054528.
The Qizhi Kebitong formula (QKF) has been utilized as a traditional Chinese medicine (TCM) remedy for over two decades in treating diabetic peripheral neuropathy (DPN) with notable clinical efficacy. However, its precise mechanism and bioactive constituents remain elusive.
Through ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) analysis was used to identify the primary components of QKF. Nerve conduction function in mice was assessed by measuring sensory thresholds and nerve conduction velocities. Laser speckle contrast imaging (LSCI) was used to examine the effect of QKF on foot pads and perineural blood flow in mice. Additionally, Transmission electron microscopy (TEM) and various pathologic stains were utilized to observe QKF's therapeutic effect on sciatic nerve (SN) damage in DPN mice. The impact of QKF on the pathological mechanism of the DPN model was explored through qRT-PCR, Western blot, and immunohistochemistry.
Our results demonstrated that QKF improved phenotypic features in a mouse model of DPN, increased blood flow around the foot pad and SN, and somewhat repaired the pathological structure and function of SN. Furthermore, the study revealed that QKF slowed down the progression of DPN by inhibiting the endoplasmic reticulum (ER) stress apoptosis signaling pathway mediated by PERK/ATF4/CHOP pathway.
The significant neuroprotective effects of QKF in experimental DPN mice were confirmed by our findings, which offer important scientific evidence supporting its potential utilization in DPN treatment.
芪蛭柯痹通方（QKF）作为一种中药疗法，已用于治疗糖尿病周围神经病变（DPN）二十多年，临床疗效显著。然而，其确切机制和生物活性成分仍不清楚。
通过超高效液相色谱-四极杆飞行时间质谱（UHPLC/QTOF-MS）分析来鉴定QKF的主要成分。通过测量感觉阈值和神经传导速度来评估小鼠的神经传导功能。激光散斑对比成像（LSCI）用于检测QKF对小鼠脚垫和神经周围血流的影响。此外，利用透射电子显微镜（TEM）和各种病理染色来观察QKF对DPN小鼠坐骨神经（SN）损伤的治疗效果。通过qRT-PCR、蛋白质免疫印迹法和免疫组织化学来探讨QKF对DPN模型病理机制的影响。
我们的结果表明，QKF改善了DPN小鼠模型的表型特征，增加了脚垫和SN周围的血流量，并在一定程度上修复了SN的病理结构和功能。此外，研究还表明，QKF通过抑制由PERK/ATF4/CHOP途径介导的内质网（ER）应激凋亡信号通路来减缓DPN的进展。
我们的研究结果证实了QKF在实验性DPN小鼠中具有显著的神经保护作用，为其在DPN治疗中的潜在应用提供了重要的科学证据。
