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萍乡市第二人民医院神经外科,江西 萍乡 337000
Published:30 October 2023,
Received:04 January 2023,
Revised:01 September 2023,
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易宇光,刘昌平,何佳佳.基于Nrf2/HO-1信号通路探讨虾青素对创伤性脑损伤模型大鼠氧化应激和炎症反应的影响 Δ[J].中国药房,2023,34(20):2490-2496.
YI Yuguang,LIU Changping,HE Jiajia.Effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury based on Nrf2/HO-1 signaling pathway[J].ZHONGGUO YAOFANG,2023,34(20):2490-2496.
易宇光,刘昌平,何佳佳.基于Nrf2/HO-1信号通路探讨虾青素对创伤性脑损伤模型大鼠氧化应激和炎症反应的影响 Δ[J].中国药房,2023,34(20):2490-2496. DOI: 10.6039/j.issn.1001-0408.2023.20.08.
YI Yuguang,LIU Changping,HE Jiajia.Effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury based on Nrf2/HO-1 signaling pathway[J].ZHONGGUO YAOFANG,2023,34(20):2490-2496. DOI: 10.6039/j.issn.1001-0408.2023.20.08.
目的
2
探讨虾青素对创伤性脑损伤(TBI)大鼠氧化应激和炎症反应的影响。
方法
2
将雄性SD大鼠分为假手术组、模型组、虾青素低剂量组(20 mg/kg)、虾青素高剂量组(40 mg/kg)、虾青素+ML385组[虾青素40 mg/kg+核转录因子红系2相关因子2(Nrf2)抑制剂ML385 30 mg/kg],每组14只。除假手术组外,其余各组大鼠按改良的Feeney自由落体撞击法复制TBI大鼠模型。各药物组大鼠灌胃或腹腔注射相应药液,假手术组和模型组大鼠灌胃等体积生理盐水。分别于药物干预后第1、3、7天对各组大鼠的神经功能进行评分;于药物干预后第7天,观察各组大鼠脑组织形态学变化并进行炎症浸润评分,观察其脑组织神经细胞超微结构,检测脑组织中氧化应激指标[超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、一氧化氮(NO)]、炎症反应指标[肿瘤坏死因子α、白细胞介素1β(IL-1β)、IL-6、诱导型一氧化氮合酶]含量和Nrf2、血红素加氧酶1(HO-1)、NAD(P)H醌氧化还原酶1(NQO1)蛋白及mRNA的表达情况。
结果
2
与假手术组比较,模型组大鼠脑组织水肿明显并伴有大量炎症细胞浸润,神经细胞的细胞器形态受损、数量减少且超微结构破损严重;其神经功能评分,脑组织中SOD、CAT、GSH-Px、NO含量和Nrf2、HO-1、NQO1蛋白及mRNA的相对表达水平均显著降低,炎症浸润评分、MDA含量和炎症反应指标含量均显著升高(
P
<0.05)。与模型组比较,低、高剂量虾青素可显著改善脑组织及神经细胞的病理状态和神经功能评分(虾青素低剂量组药物干预第1天除外),可剂量依赖性地升高脑组织中SOD、CAT、GSH-Px、NO含量和Nrf2、HO-1、NQO1蛋白及mRNA的相对表达水平,降低炎症浸润评分、MDA含量和炎症反应指标含量(
P
<0.05);而ML385可显著抑制虾青素的上述作用(
P
<0.05)。
结论
2
虾青素可能通过激活Nrf2/HO-1信号通路而减轻TBI大鼠的氧化应激,缓解其神经功能损伤,降低炎症反应水平。
OBJECTIVE
2
To investigate the effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury (TBI).
METHODS
2
Male SD rats were randomly divided into sham operation group, model group, astaxanthin low-dose group (20 mg/kg), astaxanthin high-dose group (40 mg/kg), astaxanthin+ML385 group [astaxanthin 40 mg/kg+nuclear factor-erythroid 2-related factor 2 (Nrf2) inhibitor ML385 30 mg/kg], with 14 rats in each group. Except for the sham operation group, TBI model was induced by the modified Feeney free-fall impact method in other groups. The rats in each drug group were given the corresponding drug intragastrically or intraperitoneally, and the rats in the sham operation group and model group were intragastrically given a constant volume of normal saline. The neurological function of rats in each group was scored on the 1st, 3rd and 7th day after drug intervention; on the 7th day of drug intervention, the changes of cerebral histomorphology and inflammatory infiltration score were observed in each group, and the ultrastructure of nerve cells in brain tissue was also observed. The contents of oxidative stress indexes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO)] and inflammatory reaction indexes [tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase] as well as protein and mRNA expressions of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were detected in cerebral tissue.
RESULTS
2
Compared with the sham operation group, the brain edema of rats in the model group was obvious, accompanied by a large number of inflammatory cells infiltrated, the shape of organelles was damaged and their number was reduced, and the ultrastructure of nerve cells was seriously damaged. The neurological function score, the contents of SOD, CAT, GSH-Px and NO and the relative expression levels of Nrf2, HO-1 and NQO1 protein and mRNA in brain tissue were significantly decreased, while the inflammatory infiltration scores, the contents of MDA and inflammatory reaction indexes were significantly increased (
P
<0.05). Compared with the model group, low-dose and high-dose astaxanthin could significantly improve the pathological status of brain tissue and nerve cells and neurological function scores (except for the first day of drug intervention in the astaxanthin low-dose group), increase the contents of SOD, CAT, GSH-Px and NO and the relative expression levels of Nrf2, HO-1, NQO1 protein and mRNA in brain tissue in a dose-dependent manner, and reduce inflammatory infiltration scores, the contents of MDA and inflammatory reaction indexes (
P
<0.05). ML385 could significantly inhibit the above effects of astaxanthin (
P
<0.05).
CONCLUSIONS
2
Astaxanthin may reduce the oxidative stress of TBI model rats, alleviate the neurological damage and reduce the level of inflammation reaction by activating the Nrf2/HO-1 signaling pathway.
虾青素创伤性脑损伤氧化应激炎症反应核转录因子红系2相关因子2/血红素加氧酶1信号通路
traumatic brain injuryoxidative stressinflammatory reactionNrf2/HO-1 signaling pathway
GALGANO M,TOSHKEZI G,QIU X C,et al. Traumatic brain injury:current treatment strategies and future endeavors[J]. Cell Transplant,2017,26(7):1118-1130.
KHELLAF A,KHAN D Z,HELMY A. Recent advances in traumatic brain injury[J]. J Neurol,2019,266(11):2878-2889.
郑琳,候鹏飞,周曦,等. 虾青素在中枢神经系统疾病防治中的实验研究进展[J]. 现代预防医学,2017,44(24):4497-4500,4516.
ZHENG L,HOU P F,ZHOU X,et al. Experimental research progress of astaxanth in prevention and treatment of central nervous system diseases[J]. Mod Prev Med,2017,44(24):4497-4500,4516.
ZHANG X S,LU Y,LI W,et al. Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/NRF2/Prx2/ASK1/p38 after traumatic brain injury in mice[J]. Br J Pharmacol,2021,178(5):1114-1132.
林良烽. 虾青素对缺氧缺血性脑损伤新生大鼠模型的神经保护作用[J]. 中国组织工程研究,2015,19(40):6480-6484.
LIN L F. The neuroprotective effect of astaxanthin on newborn rat models of hypoxic-ischemic brain damage[J]. Chin J Tissue Eng Res,2015,19(40):6480-6484.
KHATRI N,THAKUR M,PAREEK V,et al. Oxidative stress:major threat in traumatic brain injury[J]. CNS Neurol Disord Drug Targets,2018,17(9):689-695.
顾媛媛,张淑香,周忠光,等. 基于Nrf2/HO-1信号通路探讨益气活血方对脑缺血损伤大鼠氧化应激反应的影响[J]. 中国实验方剂学杂志,2019,25(24):30-35.
GU Y Y,ZHANG S X,ZHOU Z G,et al. Effect of Yiqi huoxue recipe on oxidative stress response in rats with cerebral ischemia injury based on Nrf2/HO-1 signaling pathway[J]. Chin J Exp Tradit Med Formulae,2019,25(24):30-35.
谢婷,颜雅婷,陈文奕,等. 虾青素激活Nrf2/HO-1通路对蓝光损伤视锥细胞的保护作用[J]. 中国现代应用药学,2022,39(1):36-41.
XIE T,YAN Y T,CHEN W Y,et al. Protective effects of astaxanthin on blue light damaged cones through activa-ting Nrf2/HO-1 pathway[J]. Chin J Mod Appl Pharm,2022,39(1):36-41.
胡戈,曹建民,周海涛,等. 虾青素介导Nrf2信号通路减轻大强度运动诱导大鼠心肌细胞的凋亡[J]. 食品工业科技,2019,40(8):266-271.
HU G,CAO J M,ZHOU H T,et al. Astaxanthin reduces myocardial cell apoptosis induced by high intensity trai-ning via activating Nrf2 in rats[J]. Sci Technol Food Ind,2019,40(8):266-271.
陈澜,石京山,龚其海,等. 淫羊藿苷对大鼠创伤性脑损伤后白细胞介素1β和肿瘤坏死因子α的作用[J]. 中国新药与临床杂志,2017,36(4):210-214.
CHEN L,SHI J S,GONG Q H,et al. Effects of icariin on IL-1β and TNF-α after traumatic brain injury in rats[J]. Chin J New Drugs Clin Remedies,2017,36(4):210-214.
侯晓宁,张育昆,陈祉晴,等. 虾青素对D-半乳糖致衰老大鼠肾脏和心脏组织氧化损伤的修复作用[J]. 现代食品科技,2022,38(12):146-153.
HOU X N,ZHANG Y K,CHEN Z Q,et al. Protective effects of astaxanthin against oxidative damage of the kidney and heart tissues in D-galactose induced aging rats[J]. Mod Food Sci Technol,2022,38(12):146-153.
张蕾,冷玉芳,张天雪,等. Nrf2/HO-1信号通路在阿托伐他汀减轻小鼠肠缺血再灌注损伤中的作用[J]. 中华麻醉学杂志,2021,41(6):685-689.
ZHANG L,LENG Y F,ZHANG T X,et al. Role of Nrf2/HO-1 signaling pathway in atorvastatin-induced reduction of intestinal ischemia-reperfusion injury in mice[J]. Chin J Anesthesiol,2021,41(6):685-689.
胡晓芳,郑少锐,聂群,等. 英夫利昔单抗对创伤性脑损伤后神经功能的保护作用及机制研究[J]. 中华神经医学杂志,2022,21(6):563-572.
HU X F,ZHENG S R,NIE Q,et al. Protective effect of infliximab on neurological function and its related mechanism in mice after traumatic brain injury[J]. Chin J Neuromed,2022,21(6):563-572.
刘菲. Ghrelin调控炎性小体活化途径对实验性自身免疫性脑脊髓炎的神经保护作用及机制研究[D]. 沈阳:中国医科大学,2020.
LIU F. The experimental study of the neuroprotective effect of ghrelin on experimental autoimmune encephalomye-litis involving inflammasome activation[D]. Shenyang:China Medical University,2020.
CAPIZZI A,WOO J,VERDUZCO-GUTIERREZ M. Traumatic brain injury:an overview of epidemiology,pathophysiology,and medical management[J]. Med Clin North Am,2020,104(2):213-238.
WANG H,ZHOU X M,WU L Y,et al. Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury[J]. J Neuroinflammation,2020,17(1):188.
徐伟,谢之易,王泽旭,等. 核因子E2相关因子2对脑出血继发性损伤调控机制研究进展[J]. 中国现代神经疾病杂志,2022,22(10):836-840.
XU W,XIE Z Y,WANG Z X,et al. The role of Nrf2 in the secondary brain injury after intracerebral hemorrhage[J]. Chin J Contemp Neurol Neurosurg,2022,22(10):836-840.
郭新明,吴丽君,赵静,等. 虾青素补充与急性大强度运动对机体Nrf2抗氧化通路影响的研究[J]. 山东体育学院学报,2020,36(6):111-118.
GUO X M,WU L J,ZHAO J,et al. Effect of astaxanthin supplementation and acute high-intensity exercise on the antioxidant pathway of Nrf2[J]. J Shandong Sport Univ,2020,36(6):111-118.
周子薇,郑晓梅,先耀,等. 虾青素对脑出血大鼠的神经保护作用及机制[J]. 山东医药,2020,60(26):6-9.
ZHOU Z W,ZHENG X M,XIAN Y,et al. Neuroprotective effect and mechanism of astaxanthin on rats with intracerebral hemorrhage[J]. Shandong Med J,2020,60(26):6-9.
张启财,张赛,王永阁,等. Exendin-4对颅脑创伤大鼠认知功能及Nrf2信号通路的影响[J]. 中华行为医学与脑科学杂志,2019,28(1):33-37.
ZHANG Q C,ZHANG S,WANG Y G,et al. Effects of exendin-4 on cognitive function and Nrf2 signaling pathway in rats with traumatic brain injury[J]. Chin J Behav Med Brain Sci,2019,28(1):33-37.
赵万里,詹世钦,陈江生,等. 葛根素对创伤性脑损伤大鼠抗凋亡影响的机制分析[J]. 中国社区医师,2019,35(21):6-7.
ZHAO W L,ZHAN S Q,CHEN J S,et al. Mechanism analysis of the effect of puerarin on anti-apoptosis in rats with traumatic brain injury[J]. Chin Community Dr,2019,35(21):6-7.
陈江生,陈保东,凌毕益,等. 葛根素通过Nrf2-ARE信号通路抵抗氧化应激对创伤性脑损伤的神经保护作用[J]. 卒中与神经疾病,2017,24(2):91-94.
CHEN J S,CHEN B D,LING B Y,et al. Puerarin protects traumatic brain injury through Nrf2-ARE pathway to resist oxidative stress[J]. Stroke Nerv Dis,2017,24(2):91-94.
李佳蕊,罗本燕. 神经炎症反应在动物创伤性脑损伤中的研究进展[J]. 国际神经病学神经外科学杂志,2019,46(2):214-217.
LI J R,LUO B Y. Research progress of neuroinflammatory reaction in traumatic brain injury in animals[J]. J Int Neurol Neurosurg,2019,46(2):214-217.
王星,余万,黄保胜. 异甘草素通过TLR4-TBK1-IKKε信号通路对创伤性脑损伤大鼠脑内炎症反应的影响[J]. 安徽医科大学学报,2021,56(2):277-282.
WANG X,YU W,HUANG B S. Effect of isoliquiritigenin on the brain inflammation with traumatic brain injury in rat via TLR4-TBK1-IKKε signaling pathway[J]. Acta Univ Med Anhui,2021,56(2):277-282.
张茹,曲中原,杜娟. 葡萄籽原花青素通过Nrf2/HO-1通路减轻镉诱导的幼龄大鼠认知功能损伤[J]. 中药药理与临床,2021,37(4):32-36.
ZHANG R,QU Z Y,DU J. Proanthocyanidins in grape seeds protects against cadmium-induced cognitive impairment in young rats by regulating Nrf-2/HO-1 pathway[J]. Pharmacol Clin Chin Mater Med,2021,37(4):32-36.
郭瑞俊,郭佩俊,韩云彪,等. 基于氧化应激探讨Nrf2/HO-1信号通路与临床疾病关系研究进展[J]. 河北医药,2022,44(20):3157-3162.
GUO R J,GUO P J,HAN Y B,et al. Research progress on the correlation between Nrf2/HO-1 signal pathway and clinical diseases based on oxidative stress[J]. Hebei Med J,2022,44(20):3157-3162.
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