背景：糖尿病性神经病（DN）是一种严重的微血管并发症，是糖尿病发病和死亡的主要原因。它的特征是末梢感觉神经纤维的神经变性伴随随后的疼痛，失去感觉，和感觉异常,从而影响糖尿病患者的生活质量。它被认为是全球非创伤性截肢的主要原因，反映了当前疗法的不足。普拉克索(PPX)是一种用于治疗帕金森病的多巴胺受体激动剂。本研究旨在探讨PPX在DN实验模型中的潜在神经保护作用。
方法:SD大鼠随机分为5组:正常对照组,正常+PPX（1mg/kg）组，STZ控制,STZ+PPX(0.25和1mg/kg/天,持续8周)。从坐骨神经组织学改变方面评估PPX对大鼠的神经保护作用，氧化应激，TLR4/MyD88/IRAK-1/TRAF-6/NF-κB轴及下游炎症介质的蛋白表达。
结果：PPX给药改善了神经元炎症和细胞凋亡的组织病理学征象。此外,PPX减弱STZ诱导的坐骨神经氧化应激并下调TLR4，MyD88，IRAK-1，TRAF-6，NF-κB和下游介质的神经组织表达（TNF-α，IL-1β和ICAM-1）。
结论：总的来说，本研究揭示了PPX作为缓解糖尿病患者神经病变进展的潜在保护性药物.PPX神经保护作用可归因于调节神经组织中的TLR4/MyD88/IRAK-1/TRAF-6/NF-κB轴信号传导，随后减轻氧化应激和炎症。
BACKGROUND: Diabetic neuropathy (DN) is a serious microvascular complication and a major cause of morbidity and mortality in diabetes mellitus. It is characterized by neurodegeneration of terminal sensory nerve fibers with subsequent pain, loss of sensation, and paresthesia, thus compromising the quality of life of diabetic patients. It is considered the leading cause of non-traumatic amputations worldwide, reflecting the insufficiency of current therapies. Pramipexole (PPX) is a dopamine receptor agonist used for the treatment of Parkinson\'s disease. The current study aims to investigate the potential neuroprotective effect of PPX in an experimental model of DN.
METHODS: Sprague Dawley rats were randomly assigned into five groups: normal control, Normal + PPX (1 mg/kg) group, STZ control, STZ + PPX (0.25 and 1 mg/kg/day for eight weeks). The neuroprotective effect of PPX in rats was evaluated in terms of sciatic nerve histological alterations, oxidative stress, and protein expression of TLR4/MyD88/IRAK-1/TRAF-6/NF-κB axis and downstream inflammatory mediators.
RESULTS: PPX administration ameliorated histopathological signs of neuronal inflammation and apoptosis. Additionally, PPX attenuated STZ-induced sciatic nerve oxidative stress and downregulated neural tissue expression of TLR4, MyD88, IRAK-1, TRAF-6, NF-κB and downstream mediators (TNF-α, IL-1β and ICAM-1).
CONCLUSIONS: Collectively, the current study sheds light on PPX as a potential protective medication to alleviate neuropathy progression in diabetic patients. PPX neuroprotective effect can be attributed to modulating TLR4/ MyD88/IRAK-1/TRAF-6/ NF-κB axis signaling in nerve tissues with subsequent attenuation of oxidative stress and inflammation.
