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.
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。