褪黑素通过缓解氧化应激促进糖尿病周围神经病变神经修复的作用机制OA

Objective To investigate the mechanisms by which melatonin promotes nerve repair in diabetic peripheral neu-ropathy.Methods Sprague-Dawley rats were divided into a control group,a model group,and a melatonin treatment group.Diabetic peripheral neuropathy was induced by intraperitoneal injection of streptozotocin(60 mg/kg).Rats in the melatonin treatment group re-ceived melatonin(10 mL/kg,intraperitoneally).Dorsal root ganglia tissues were collected,and hematoxylin-eosin staining was used to observe morphological changes in neurons.The mRNA and protein expression levels of mitochondrial fusion protein 2(Mfn2),dy-namin-related protein 1(DRP1),glucose-regulated protein 78(Grp78),PTEN-induced kinase 1(Pink1),protein kinase R-like en-doplasmic reticulum kinase(PERK),phosphorylated p47 phox(p47),neurotrophin(NT),and nerve growth factor(NGF)were de-tected by Real-time quantitative polymerase chain reaction and Western blot.In vitro,DRG neurons were treated with high glucose to establish a cellular injury model,while the melatonin treatment group received melatonin(0.5 mmol/L).Reactive oxygen species(ROS)levels were measured using assay kits,mitochondrial membrane potential(MMP)was assessed by JC-1 staining,and Ca2+lev-els were detected with fluorescent probes.The expression of Mfn2,DRP1,Pink1,Grp78,PERK,p47,NT,and NGF were examine.Results The successful establishment of diabetic peripheral neuropathy model was verified by blood glucose levels>16.7 mmol/L and decreased sensory conduction velocity of caudal nerve.Compared with the control group,dorsal root ganglia neurons in the model group showed indistinct nuclear-cytoplasmic boundaries,and pale cytoplasm,while neuronal morphology was relatively restored in the melatonin group.In the model group,mRNA and protein levels of DRP1,Grp78,PERK,p47,NT,and NGF were significantly in-creased,whereas those of Mfn2 and Pink1 were decreased(P<0.05),the mRNA and protein expression levels were improved in the melatonin treatment group(P<0.05).In vitro,compared with the control group,high-glucose-treated dorsal root ganglia neurons showed increased ROS levels,decreased MMP and Ca2+levels,upregulation of DRP1,Grp78,PERK,p47,NT,and NGF,and downregulation of Mfn2 and Pink1(P<0.05).In contrast,melatonin treatment reduced ROS levels,increased MMP and Ca2+levels,upregulated Mfn2 and Pink1,and downregulated DRP1,Grp78,PERK,p47,NT,and NGF(P<0.05).Conclusion Melatonin al-leviates mitochondrial function and promotes nerve repair in diabetic peripheral neuropathy by modulating the expression of proteins in-volved in endoplasmic reticulum stress and oxidative stress.These findings suggest that melatonin has potential therapeutic value in the management of diabetic peripheral neuropathy.