西安交通大学学报（医学版）2025，Vol.46Issue(4)：606-615,10.DOI:10.7652/jdyxb202504009
虾青素通过抗氧化作用缓解奥沙利铂诱发的神经病理性痛
Astaxanthin reduces oxaliplatin-induced neuropathic pain through antioxidant mechanisms
摘要
Abstract
Objective To investigate the mechanisms by which astaxanthin(AST)alleviates oxaliplatin(OXA)-induced neuropathic pain through antioxidant pathways so as to provide theoretical basis for clinical intervention.Methods Animal experiments:SD rats were divided into five groups(n=6):control group,OXA(4 mg/kg)group,OXA+Oil group,OXA+AST(5 mg/kg)group,and OXA+AST(10 mg/kg)group.Mechanical and cold pain thresholds were measured at day 0,7,14,and 21.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in the dorsal root ganglia(DRG)were detected using the thiobarbituric acid(TBA)method and WST-1 assay,respectively.Western blotting was performed to analyze the expressions of Nrf2 and HO-1.Cell experiments:neuro-2a cells were divided into control group,OXA(50 μmol/L)group,AST(10 μmol/L)group,and OXA(50 μmol/L)+AST(10 μmol/L)group.Cells were treated with nerve growth factor(NGF,50 ng/mL)to induce growth,and morphological changes were observed under an inverted microscope.Intracellular reactive oxygen species(ROS)level and mitochondrial superoxide were measured using DCFH-DA fluorescent probe and MitoSOXTM red,respectively.Mitochondrial function was assessed by JC-1 assay.Western blotting was used to detect Nrf2 and HO-1 expressions.Results Animal experiments:① Mechanical and cold pain thresholds were reduced in OXA and OXA+Oil groups(P＜0.05),while AST significantly increased these thresholds in OXA-treated rats(P＜0.05).② SOD activity decreased while MDA content increased in the DRG of OXA-treated rats(P＜0.05).AST restored SOD activity and reduced MDA level(P＜0.05,P＜0.01).③ Western blotting showed elevated Nrf2 and HO-1 expressions in OXA group(P＞0.05),which were further upregulated by AST(P＜0.05,P＜0.01).Cell experiments:① OXA reduced the number of neurite-bearing cells and shortened the average neurite length(P＜0.05).Inverted microscopic observation revealed that AST intervention increased both parameters(P＜0.01,P＜0.001).② OXA increased intracellular and mitochondrial ROS fluorescence intensity(P＜0.05),which was attenuated by AST(P＜0.01).③ JC-1 assay revealed decreased mitochondrial membrane potential in OXA group(P＜0.01),which was partially reversed by AST(P＜0.05).④ Western blotting results showed that OXA upregulated Nrf2 and HO-1 expressions(P＜0.05,P＜0.01),and AST further enhanced their levels(P＜0.01).Conclusion AST alleviates OXA-induced neuropathic pain by promoting Nrf2/HO-1 expression,enhancing SOD activity,reducing lipid peroxidation and ROS production,and improving mitochondrial function.关键词
虾青素(AST)/奥沙利铂(OXA)/神经病理性痛/氧化应激Key words
astaxanthin(AST)/oxaliplatin(OXA)/neuropathic pain/oxidative stress分类
医药卫生引用本文复制引用
陈冲,田俊杰,周瓒,高瑞娟,唐雪纯,高逸璇,马克涛,李丽,司军强..虾青素通过抗氧化作用缓解奥沙利铂诱发的神经病理性痛[J].西安交通大学学报（医学版）,2025,46(4):606-615,10.基金项目
国家自然科学基金资助项目(No.81560081) （No.81560081）
兵团财政科技计划项目(No.2020AB019) （No.2020AB019）
Supported by the National Natural Science Foundation of China(No.81560081)and Bingtuan Financial Science and Technology Plan Project(No.2020AB019) （No.81560081）
