基于Nrf2/ARE通路探讨脑安滴丸干预疲劳状态下偏头痛的作用及其氧化应激机制
Efficacy of Naoan Dropping Pill on the intervention of migraine under fatigue state and the mechanism of oxidative stress based on Nrf2/ARE pathway
- 北京中医药 2022年41卷第7期 页码：713-719
- 作者机构：
1.北京中医药大学,北京 100029
2.北京中医药大学东直门医院脑病科,北京 100700
3.北京中医药大学中医脑病研究院,北京 100700
- 作者简介：
樊欢欢，女，30岁，博士。研究方向：中医药防治脑血管病。
曹克刚， E-mail：kgdoctor@sina.com
- 基金信息：国家科技重大专项(2017ZX09304019)
DOI：10.16025/j.1674-1307.2022.07.003
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樊欢欢，刘珍洪，曹克刚.基于Nrf2/ARE通路探讨脑安滴丸干预疲劳状态下偏头痛的作用及其氧化应激机制［J］.北京中医药，2022，41（7）：713-719.
FAN Huan-huan,LIU Zhen-hong,CAO Ke-gang.Efficacy of Naoan Dropping Pill on the intervention of migraine under fatigue state and the mechanism of oxidative stress based on Nrf2/ARE pathway[J]. Beijing Journal of Traditional Chinese Medicine,2022,41(07):713-719.
樊欢欢，刘珍洪，曹克刚.基于Nrf2/ARE通路探讨脑安滴丸干预疲劳状态下偏头痛的作用及其氧化应激机制［J］.北京中医药，2022，41（7）：713-719. DOI： 10.16025/j.1674-1307.2022.07.003.
FAN Huan-huan,LIU Zhen-hong,CAO Ke-gang.Efficacy of Naoan Dropping Pill on the intervention of migraine under fatigue state and the mechanism of oxidative stress based on Nrf2/ARE pathway[J]. Beijing Journal of Traditional Chinese Medicine,2022,41(07):713-719. DOI： 10.16025/j.1674-1307.2022.07.003.
摘要
目的,2,探讨疲劳状态下偏头痛大鼠体内的氧化应激状态，及脑安滴丸对氧化应激经典信号通路核转录因子红系2相关因子2（Nrf2）/抗氧化反应元件（ARE）的调控作用。,方法,2,将60只大鼠随机分为空白对照组（空白组）、硝酸甘油模型组（NTG模型组）、疲劳状态下NTG模型组（F⁃NTG模型组）、氟桂利嗪硝酸甘油组（NTG+氟桂利嗪组）、脑安滴丸硝酸甘油组（NTG+脑安滴丸组）、脑安滴丸疲劳状态下硝酸甘油组（F⁃NTG+脑安滴丸组）6组。预防性给予大鼠药物干预7 d，在给药第6天通过腹腔注射聚肌苷酸-聚胞苷酸（polyI：C）模拟疲劳状态，次日颈部皮下注射硝酸甘油注射液，复制偏头痛大鼠模型，分别在造模前后进行大鼠机械痛阈、热痛阈测试，造模成功后检测大鼠血清中氧化应激相关指标丙二醛（MDA）、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）的含量，及三叉神经脊束核中偏头痛疗效相关蛋白降钙素基因相关肽（CGRP）、c⁃Fos、氧化应激机制相关蛋白Nrf2、血红素加氧酶（HO）⁃1的表达情况。,结果,2,NTG模型组、F⁃NTG模型组的机械痛阈、热痛阈较空白组明显降低（,P,<,0.01），给予脑安滴丸干预后，NTG+脑安滴丸组及F⁃NTG+脑安滴丸组机械痛阈及热痛阈较其相应模型组均有明显升高（,P,<,0.05）。NTG模型组、F⁃NTG模型组大鼠血清MDA、SOD、GSH水平均较空白组升高（,P,<,0.01），给予脑安滴丸干预后，NTG+脑安滴丸组及F⁃NTG+脑安滴丸组较其相应模型组血清MDA水平下降（,P,<,0.01），SOD、GSH水平进一步升高（,P,<,0.05）。NTG模型组、F⁃NTG模型组大鼠三叉神经脊束核中CGRP、c⁃Fos、Nrf2、HO⁃1蛋白表达量均较空白组增多（,P,<,0.05），给予脑安滴丸干预后，NTG+脑安滴丸组及F⁃NTG+脑安滴丸组较其相应模型组CGRP、c⁃Fos蛋白表达量均有不同程度降低（,P,<,0.01），但Nrf2、HO⁃1蛋白表达量均有明显升高（,P,<,0.01）。,结论,2,硝酸甘油注射液诱导的偏头痛模型大鼠体内存在氧化应激反应，抗氧化通路Nrf2/ARE被激活，疲劳状态可以加重偏头痛模型大鼠体内的氧化应激状态；脑安滴丸对偏头痛及疲劳状态下偏头痛大鼠有一定的治疗作用，同时可以提高大鼠体内抗氧化酶的活性，降低脂质过氧化物水平，改善氧化应激状态。
Abstract
Objective,2,To investigate the oxidative stress state in migraine rats under fatigue state and the regulation effect of Naoan Dropping Pill on Nrf2/ARE signaling pathway of oxidative stress.,Methods,2,Prophylactic drug intervention was given to rats for 7 days.On the 6th day of administration，the fatigue state was simulated by intraperitoneal injection of polyI：C，and nitroglycerin was injected subcutaneously into the neck on the 7th day to create migraine model.Mechanical pain threshold，thermal pain threshold and grasping force were tested before and after modeling.After successful molding，the contents of MDA，GSH and SOD related indicators of oxidative stress in serum，and the expression of migraine efficacy related proteins CGRP，c⁃Fos and oxidative stress mechanism-related proteins Nrf2 and HO⁃1 in the trigeminal spinal tract nucleus were detected.,Results,2,Mechanical pain threshold and thermal pain threshold in NTG model group and F⁃NTG model group were significantly lowered than those in blank group （,P,<,0.01），and after the intervention of Naoan Dropping Pill，the mechanical pain threshold and thermal pain threshold in the intervention group were significantly increased than those in the model group（,P,<,0.05）.The serum MDA level of NTG model group and F⁃NTG model group was increased than that of blank group（,P,<,0.01），SOD and GSH levels were increased than those in blank group（,P ,<, 0.01）.After the intervention of Naoan Dropping Pill，the serum MDA level in the intervention group was lowered than that in the model group（,P,<,0.01）.The levels of SOD and GSH further increased（,P,<,0.05）.The expression levels of CGRP and c⁃Fos protein in the trigeminal spinal nucleus of rats in NTG model group and F⁃NTG model group were increased than those in blank group（,P,<,0.05）.Compared with the model group，the expression levels of CGRP and c⁃Fos protein in the trigeminal spinal nucleus of the intervention group were decreased to various degrees after the intervention of Naoan Dropping Pill（,P,<,0.01）.The expression of Nrf2 and HO⁃1 protein in the trigeminal spinal nucleus of rats in NTG model group and F⁃NTG model group was increased than that in blank group（,P,<,0.05）.Compared with the model group，the expression levels of Nrf2 and HO⁃1 protein in the trigeminal spinal nucleus of the intervention group were significantly increased after the intervention of Naoan Dropping Pill（,P,<,0.01）.,Conclusion,2,There was oxidative stress response in NTG-induced migraine model rats，and the antioxidant defense pathway NRF2/ARE was activated.Fatigue state can aggravate oxidative stress in migraine rats.Naoan Dropping Pill has a certain therapeutic effect on migraine in rats under fatigue state，and can improve the oxidative stress state in migraine rats.
关键词
脑安滴丸偏头痛疲劳氧化应激大鼠
Keywords
Naoan Dropping Pillmigrainefatigueoxidative stressrats
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