[1]郑思敏,张少博,牛晓丽△,等.川芎嗪通过激活PKCα/Nrf2信号转导抑制七氟烷诱导的氧化损伤和血脑屏障破坏研究*[J].陕西中医,2020,(8):1025-1031.[doi:DOI:10.3969/j.issn.1000-7369.2020.08.004]
　ZHENG Simin,ZHANG Shaobo,NIU Xiaoli,et al.Ligustrazine inhibits sevoflurane-induced oxidative damage and blood-brain barrier disruption by activating PKCα/Nrf2 signaling[J].,2020,(8):1025-1031.[doi:DOI:10.3969/j.issn.1000-7369.2020.08.004]
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川芎嗪通过激活PKCα/Nrf2信号转导抑制七氟烷诱导的氧化损伤和血脑屏障破坏研究*
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2020年8期
页码:
1025-1031
栏目:
基础研究
出版日期:
2020-08-05

文章信息/Info

Title:
Ligustrazine inhibits sevoflurane-induced oxidative damage and blood-brain barrier disruption by activating PKCα/Nrf2 signaling
作者:
郑思敏; 张少博; 牛晓丽△; 刘鸿涛; 熊虹飞; 张会娟
西安交通大学第二附属医院麻醉科(西安 710004)
Author(s):
ZHENG Simin; ZHANG Shaobo; NIU Xiaoli; et al.
Department of Anesthesiology,The Second Affiliated Hospital of Xi'an Jiaotong University(Xi'an 710004)
关键词:
川芎嗪;  海马;  蛋白激酶C;  七氟烷;  小鼠;  动物实验
Keywords:
Ligustrazine;  Hippocampus;  Protein kinase C;  Sevoflurane;  Mice;  Animal experimentation
分类号:
R614
DOI:
DOI:10.3969/j.issn.1000-7369.2020.08.004
文献标志码:
A
摘要:
目的:研究川芎嗪对七氟烷引起的氧化损伤以及血脑屏障(BBB)生理功能损伤的影响及其机制。方法:将新生幼鼠随机分组,设置对照组,并分别使用七氟烷、七氟烷和溶剂、七氟烷和川芎嗪处理小鼠,暴露于七氟烷中不同时长处死并收集小鼠大脑和海马组织,通过免疫酶联吸附检测ROS,SOD,MDA,GSH和S100β蛋白水平,制作小鼠大脑和海马组织切片并通过免疫化学染色和免疫荧光染色检测小鼠大脑和海马组织中MMP-2、MMP-9、TIMP-1、TIMP-2以及HO-1的表达,并检测Nrf2的核易位,HE染色后通过透射电子显微镜检查海马神经元损伤情况,通过蛋白质印迹分析PKC/Nrf2以及MMP-2、MMP-9表达情况,使用原位酶谱检测明胶酶活性并通过PCR检测ZO-1的表达。结果:与对照组相比,七氟烷组海马神经元损伤明显,而川芎嗪处理可以明显改善七氟烷诱导的海马神经元损伤; 与对照组相比,七氟烷处理后MMP-2、MMP-9表达和明胶酶活性明显增加,ZO-1表达明显减少,BBB通透性显著增加,而TIMP-1和TIMP-2表达无显著改变; 与七氟烷组相比,川芎嗪可以抑制明胶酶活性,促进ZO-1表达,改善BBB生理状态; 与溶剂组和七氟烷组相比,对照组和川芎嗪组ROS和BMD水平明显降低,MDA和GSH活性显著增加,PKCα、Nrf2和HO-1 的表达以及Nrf2的核易位显著增加。结论:川芎嗪可以通过PKCα/Nrf2信号通路以及抑制明胶酶活性,改善BBB通透性,保护海马免受氧化应激的伤害,改善海马体组织病理学结构。
Abstract:
Objective:To study the effect and mechanism of ligustrazine on oxidative damage induced by sevoflurane and physiological function of blood-brain barrier(BBB).Methods:The newborn pups were randomly divided into a control group and 3 other groups which were treated with sevoflurane,sevoflurane and solvent,sevoflurane and ligustrazine.There were all exposed to sevoflurane for different durations and sacrificed to collect the brain and hippocampus tissues were tested for protein levels of ROS,SOD,MDA,GSH and S100β by immunoenzyme-linked adsorption.Mice brain and hippocampal tissue sections were made and MMP-2 and MMP were detected in mouse brain and hippocampus tissue by immunochemical staining and immunofluorescence staining-9,TIMP-1,TIMP-2 and HO-1 expression,and detect the nuclear translocation of Nrf2.After HE staining,examine the damage of hippocampal neurons by transmission electron microscope,and analyze PKC/Nrf2 and MMP-2 by western blot.MMP-9 expression,using in situ zymography to detect gelatinase activity and PCR to detect ZO-1 expression.Results:Compared with the CON group,hippocampal neuron damage was significant in the sevoflurane group,and ligustrazine treatment could significantly improve hippocampal neuron damage induced by sevoflurane; compared with the CON group,MMP-2 after sevoflurane treatment,MMP-9 expression and gelatinase activity were significantly increased,ZO-1 expression was significantly reduced,BBB permeability was significantly increased,and TIMP-1 and TIMP-2 expressions were not significantly changed; compared with SEV group,ligustrazine could inhibit Gelatinase activity promotes ZO-1 expression and improves BBB physiological status.Compared with S+S and SEV groups,ROS and BMD levels in the CON group and S+L group were significantly reduced,MDA and GSH activities were significantly increased,and PKCα,Nrf2 and HO-1 expression and nuclear translocation of Nrf2 increased significantly.Conclusion:Ligustrazine can improve the BBB permeability,protect the hippocampus from oxidative stress,and improve the histopathological structure of the hippocampus through the PKCα / Nrf2 signaling pathway and inhibition of gelatinase activity.

参考文献/References:

[1] Zuo Y,Li BW,Xie JH.Lurane anesthesia during pregnancy in mice induces cognitive impairment in the offspring by causing iron deficiency and inhibiting myelinogenesis[J].Neurochemistry International,2020,135(3):112-131.
[2] Stephen I,Saiprasad R.Cytosolic Ca2+ modulates golgi structure through PKCα-Mediated GRASP55 phosphorylation[J].Science,2020,23(3):72-81.
[3] Jose RC,Ronaldo R,Caetano N.Effect of lurane on ckmb release after pci with drug-eluting stents:a randomised trial[J].Journal of the American College of Cardiology,2020,75(11):22-29.
[4] Dholakia U,Seddighi R.Pharmacokinetics of midazolam in flurane-anesthetized cats[J].Veterinary Anaesthesia and Analgesia,2020,47(2):129-135.
[5] Liu CL,Ding RW.Flurane protects against intestinal ischemia-reperfusion injury by activating peroxisome proliferator-activated receptor Gamma/Nuclear factor-κB pathway in rats[J].Pharmacology,2020,105(3):73-39.
[6] Zhu JP,Zhang ZZ,Yan QY.Metformin attenuates oflurane-induced neurocognitive impairment through AMPK-ULK1-dependent autophagy in aged mice[J].Brain Research Bulletin,2020,157(92):7-12.
[7] 蒋福勤.丹参川芎嗪联合针灸、高压氧治疗急性脑梗死的效果观察[J].中国疗养医学,2019,28(7):720-721.
[8] 张宇晶.丹参川芎嗪注射液治疗椎基底动脉供血不足头晕的效果及对椎基底动脉供血的影响探讨[J].中国医药指南,2019,17(18):184-185.
[9] He YH,Li MH,Tong GJ,et al.hPTH(3-34)(29-34)selectively activated PKC and mimicked osteoanabolic effects of hPTH(1-34)[J].Bone,2020,35(9):37-46.
[10] Liu D,Wang ZB.Silencing of PTEN inhibits the oxidative stress damage and hippocampal cell apoptosis induced by sevoflurane of lurane through activating MEK1/ERK signaling pathway in infant rats[J].Cell Cycle,2020,19(6):43-49.
[11] Sivgin V,Yalcin G,Kucuk A,et al.Effects of fullerenol nanoparticles on kidney tissue in sevoflurane of luranetreated rats[J].Bratislavske Lekarske Listy,2020,121(2):281-296.
[12] 冉 毅,张光伟,谢延风.川芎嗪对老年颅内动脉瘤夹闭术后早期脑缺血患者的影响[J].重庆医学,2014,43(24):3155-3157.
[13] Cao HL,Zhu XF,Zhang J.Dose-dependent effects of tetramethylpyrazine on the characteristics of human umbilical cord mesenchymal stem cells for stroke therapy[J].Neuroscience Letters,2020,722(10):13-22.
[14] Mini PS,Ursula B,Michael L.Atypical PKC controls β-secretase expression and thereby regulates production of Alzheimer plaque precursor Aβ in brain and insulin receptor degradation in liver[J].Metabolism,2020,104(32):59-63.
[15] 于 淼,杨万超,李文志.蛋白激酶C信号通路在血脑屏障损伤中的研究进展[J].疑难病杂志,2016,15(2):209-212.
[16] 闫 磊,胡江平,邵新然,等.淫羊藿苷联合冰片对脑缺血-再灌注损伤模型大鼠抗氧化活性、炎症反应和血脑屏障通透性影响[J].陕西中医,2018,39(12):1659-1662.
[17] 孙阳阳,孙小琴.异丙酚在血脑屏障氧糖剥夺体外模型中对紧密连接蛋白ZO-1表达的影响[J].临床医学,2016,20(1):87-92.
[18] 于 航,贾庆波.rhAng-1通过PKCα/MLC通路影响局灶性脑缺血再灌注大鼠血脑屏障通透性[J].解剖科学进展,2013,19(3):255-258.
[19] 宋江莉,袁 婕.钙拮抗剂对大鼠脑缺血后血脑屏障通透性的影响[J].陕西医学杂志,2017,46(1):5-11.
[20] 高修明,崔桂云,刘薇薇.PKCα/MLC在脑出血后脑损伤中作用机制的研究[J].脑与神经疾病杂志,2019,17(5):347-349.
[21] 张伟民,李瑞芳,付银峰,等.川芎嗪对阿霉素诱导的急性心衰小鼠心肌损伤和凋亡的保护作用[J].中国临床药理学杂志,2014,30(8):708-711.
[22] 刘延梅,马少君,苗 青,等.川芎嗪联合胚胎干细胞治疗大鼠肺纤维化的机制研究[J].陕西医学杂志,2014,43(1):10-14.
[23] 金航军.丹参川芎嗪注射液治疗椎-基底动脉供血不足性眩晕40例[J].陕西医学杂志,2012,41(6):754-755.
[24] 高美华,张 丽,李 冰,等.川芎嗪对AngⅡ诱导的大鼠心肌肥大细胞JAK-STAT通路作用[J].细胞与分子免疫学杂志,2011,27(5):519-524.

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备注/Memo

备注/Memo:
*陕西省重点研发计划项目(2017SF-180)
更新日期/Last Update: 2020-08-10