摘要
痛性糖尿病周围神经病变(painful diabetic peripheral neuropaphy,PDPN)严重威胁了糖尿病患者生命和生活质量,氧化应激和炎症反应一直被认为是痛性糖尿病周围神经病变的发病机制基石,氧化应激与炎症反应之间的交互作用是由于中文核因子κB(NF-κB)的激活以及中文核因子E2相关因子(Nrf2)的抑制,过氧亚硝酸盐中性内皮功能障碍,NO水平的改变以及巨噬细胞迁移等导致。有研究证明,Nrf2和NF-κB通路之间存在"串扰"作用,本文探讨了Nrf2-NF-κB轴在PDPN的作用。
引文
[1]Sandireddy R,Yerra VG,Areti A,et al.Neuroinflammation and oxidative stress in diabetic neuropathy:futuristic strategies based on these targets[J].Int J Endocrinol,2014,2014:674987.
[2]Negi G,Kumar A,Joshi RP,et al. Oxidative stress nd Nrf2 in the pathophysiology of diabetic neuropathy:old perspective with a new angle[J].BiochemBiophysResCommun,2011,408(1):1-5.
[3] Areti A,Yerra VG,Komirishetty P,et al. Potential therapeutic benefits of maintainingmitochondrial health in peripheral neuropathies[J].CurrNeuropharmacol,2016,14(6):593-609.
[4]Ganesh Yerra V,Negi G,Sharma SS,et al. Potential therapeutic effects of the simultaneous targeting of the Nrf2 and NF-κB pathways in diabetic neuropathy[J].Redox Biol,2013,1:394-397.
[5]Lau A,Villeneuve N F,SunZ,et al.Dual roles of Nrf2 in cancer[J].Pharmacol Res,2008,58(5/6):262-270.
[6]Lisk C,Mc Cord J,Bose S,Sullivan T,et al. Nrf2 activation:a potential strategy for the prevention of acute mountainsickness[J].Free Radic Biol Med,2013,63:264-273.
[7]Cheng D,Wu R,Guo Y,et al.Regulation of Keap1-Nrf2 signaling:The role of epigenetics[J]. Current Opinion in Toxicology,2016,1:134-138.
[8]Liu Z,XiangY,Sun G.The KCTD family of proteins:structure,function,disease relevance[J].Cell Biosci,2013,3(1):45.
[9]Kansanen E,Kuosmanen SM,Leinonen H,et al. The Keap1-Nrf2pathway:Mechanisms of activation and dysregulation in cancer[J].Redox Biology,2013,1:45-49.
[10]Wakabayashi N,Slocum SL,Skoko JJ,et al.When NRF2 talks,who's listening[J].Antioxid Redox Signal,2010,13(11):1649-1663.
[11]Dreger H,Westphal K,Weller A,et al.Nrf2-dependent upregulaton of antioxidative enzymes:a novel pathway for proteasome inhibitormediatedcardioprotection[J]. Cardiovase Res,2009,83(2):354-361.
[12]Judy B.de Haan.Nrf2 Activators as Attractive Therapeutics for Diabetic Nephropathy[J].Diabetes,2011,60(11):2683-2684.
[13]Mc Mahon M,Lamont DJ,Beattie KA,et al. Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide,zinc,and alkenals[J]. Proc Natl Acad Sci U S A,2010,107(44):18838-18843.
[14]Karin M,Yamamoto Y,Wang QM.The IKK NF-κBsystem:a treasure trove for drug development[J]. Nat Rev Drug Discov,2004,3(1):17-26.
[15]Tan Y,Ichikawa T,Li J,et al. Diabetic downregulation of Nrf2activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo[J]. Diabetes,2011,60(2):625-633.
[16]Scholz J,Woolf CJ.The neuropathic paintriad:neurons,immunecells and glia[J].NatureNeuroscience,2007,10(11):1361-1368.
[17]Singh R,Kishore L,Kaur N.Kaur.Diabetic peripheral neuropathy:current perspective and futuredirections[J]. Pharmacological Research,2014,80:21-35.
[18]Shi X,Chen Y,Nadeem L,et al.Beneficial effect of TNF-αinhibitionon diabetic peripheral neuropathy[J].Neuroinflammation,2013,10:69.
[19]Negi G,Kumar A,Sharma SS.Nrf2 and NF-κB Modulation by Sulforaphane Counteracts Multiple Manifestations of Diabetic Neuropathy in Rats and High Glucose-Induced Changes[J].Current Neurovascular Research,2011,8:294-304.
[20]Kumar A,Negi G,Sharma SS.JSH-23 targets nuclear factor-kappa B and reverses variousdeficits in experimental diabetic neuropathy:effect on neuroinflammation and antioxidant defence[J]. Diabetes Obesity and Metabolism,2011,13:750-758.
