PPARα激动剂激活Nrf2/HO-1信号通路改善肥胖大鼠神经病理性疼痛  

PPARαagonist activates Nrf2/HO-1 signaling pathway to improve neuropathic pain in obese rats

作　　者：郭欣欣 李然 张雪 宋有健 艾丽丽 GUO Xin-xin;LI Ran;ZHANG Xue;SONG You-jian;AI Li-li(Department of Pain,the Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121012,China)

机构地区：[1]锦州医科大学附属第三医院疼痛科,辽宁锦州121012

出　　处：《解剖科学进展》2020年第6期649-652,共4页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(20180550175)。

摘　　要：目的观察PPARα激动剂对肥胖大鼠神经病理性疼痛的影响,探讨Nrf2/HO-1信号通路的调控机制。方法肥胖SD大鼠分为假手术组(Sham组)、神经病理性疼痛组(CCI组)和PPARα激动剂治疗组(PPARα组)。检测大鼠热缩足反射潜伏期(TWL)和机械刺激伤害感受阈值(MWT);HE和尼氏染色观察脊髓损伤及神经元数量;ELISA检测氧化应激因子(MDA、GSH-Px和SOD)和炎症因子(TNF-α、IL-1β、IL-6)水平;Western blot和qRT-PCR检测Nrf2、HO-1和NQO1蛋白和mRNA表达。结果4PPARα激动剂可以提升CCI肥胖大鼠的TWL和MWT,改善脊髓损伤,神经元数量较CCI组明显增多,抑制炎症因子TNF-α、IL-1β、IL-6表达水平,上调CCI大鼠氧化应激因子SOD、GSH-Px含量,上调Nrf2、HO-1和NQO1表达。结论PPARα激动剂抑制神经病理性疼痛大鼠炎症及氧化应激损伤,缓解疼痛,与激活Nrf2相关。Objective To observe the effect of PPARαagonist on neuropathic pain in obese rats and explore the regulatory mechanism of Nrf2/HO-1 signaling pathway.Methods Obese SD rats were divided into sham group,neuropathic pain group(CCI group)and PPARαagonist treatment group(PPARαgroup).The values of rat thermal foot reflex latency(TWL)and mechanical stimulation nociceptive threshold(MWT)were detected,HE and Nissl staining were used to observe spinal cord injury and neuron number,ELISA was used to detect the levels of oxidative stress factors(MDA,SOD,GSH-Px)and inflammatory factors(TNF-α,IL-1β,IL-6);Western blot and qRT-PCR were used to detect Nrf2,HO-1 and NQO1 protein and mRNA expression.Results PPARαagonist increased TWL and MWT,ameliorated spinal cord injury,significantly increased the number of neurons,upregulated the content of oxidative stress factors SOD and GSHPx,increased Nrf2,HO-1 and NQO1 expression levles,but inhibited the inflammatory factor TNF-α、IL-1β、IL-6 expression level in CCI obese rats.Conclusion PPARαagonist ameliorated neuropathic pain,which is related to Nrf2 pathway activation in obese rats.

关 键 词：PPARα激动剂神经病理性疼痛 肥胖 Nrf2/HO-1信号通路 大鼠 

分 类 号：R741.02[医药卫生—神经病学与精神病学]