Improvement effect and mechanism of matrine on experimental autoimmune encephalomyelitis mice

LI Xinyu; CHU Yaojuan; DOU Mengmeng; MA Rui; LI Silu; ZHU Lin

doi:10.6039/j.issn.1001-0408.2023.10.05

您当前的位置：

首页 >

文章列表页 >

Improvement effect and mechanism of matrine on experimental autoimmune encephalomyelitis mice

更新时间：2023-05-25

- Improvement effect and mechanism of matrine on experimental autoimmune encephalomyelitis mice
- ZHONGGUO YAOFANG Vol. 34, Issue 10, Pages: 1177-1181(2023)
- 作者机构：
  
  郑州大学第一附属医院药学部，郑州　450052
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.10.05
  CLC： R965
- Published：30 May 2023，
  
  Received：20 September 2022，
  
  Revised：24 March 2023，
扫描看全文
李新雨,楚尧娟,豆萌萌等.苦参素对实验性自身免疫性脑脊髓炎小鼠的改善作用及机制 ^Δ[J].中国药房,2023,34(10):1177-1181.

LI Xinyu,CHU Yaojuan,DOU Mengmeng,et al.Improvement effect and mechanism of matrine on experimental autoimmune encephalomyelitis mice[J].ZHONGGUO YAOFANG,2023,34(10):1177-1181.
李新雨,楚尧娟,豆萌萌等.苦参素对实验性自身免疫性脑脊髓炎小鼠的改善作用及机制 ^Δ[J].中国药房,2023,34(10):1177-1181. DOI： 10.6039/j.issn.1001-0408.2023.10.05.

LI Xinyu,CHU Yaojuan,DOU Mengmeng,et al.Improvement effect and mechanism of matrine on experimental autoimmune encephalomyelitis mice[J].ZHONGGUO YAOFANG,2023,34(10):1177-1181. DOI： 10.6039/j.issn.1001-0408.2023.10.05.

摘要

目的

探讨苦参素能否通过调控铁死亡途径发挥对实验性自身免疫性脑脊髓炎（EAE）小鼠的改善作用。

方法

将30只雌性C57BL/6小鼠随机分为正常组、模型组、苦参素组，每组10只。模型组和苦参素组小鼠以含灭活结核分枝杆菌和MOG35-55的抗原乳剂诱导复制EAE模型。苦参素组小鼠自免疫后第7天开始腹腔注射苦参素注射液（50 mg/kg），正常组和模型组小鼠腹腔注射等体积生理盐水，每天1次至免疫后第18天。记录各组小鼠的神经功能学评分，以苏木精-伊红染色法和勒克斯光蓝染色法分别观察脊髓组织炎症细胞浸润和髓鞘脱失情况，以定量逆转录聚合酶链反应法和Western blot法分别检测其转铁蛋白受体1（TFR1）、核受体共激活因子4（NCOA4）、膜铁转运辅助蛋白（Heph）mRNA和胱氨酸-谷氨酸反向转运体（xCT）、谷胱甘肽过氧化物酶4（GPx4）蛋白的表达情况。

结果

与正常组比较，模型组小鼠的累计神经功能学评分显著升高（

＜0.01），脊髓组织内炎症细胞浸润和髓鞘脱失现象明显，相关评分均显著升高（

＜0.01），髓鞘组织中TFR1、NCOA4 mRNA的表达均显著上调，Heph mRNA和xCT、GPx4蛋白的表达均显著下调（

＜0.05或

＜0.01）。与模型组比较，苦参素组小鼠上述指标均显著改善（

＜0.05或

＜0.01）。

结论

苦参素对EAE小鼠有一定的改善作用，且这种作用可能与调节铁死亡中的铁代谢途径和xCT/GPx4通路有关。

Abstract

OBJECTIVE

To investigate whether matrine exerts improvement effect on experimental autoimmune encephalomyelitis （EAE） mice by regulating ferroptosis pathway.

METHODS

Totally 30 female C57BL/6 mice were randomly assigned into normal group， model group and matrine group， with 10 mice in each group. Model group and matrine group were given antigen emulsion containing inactivated

Mycobacterium tuberculosis

and MOG35-55 to induce EAE model. Matrine group was injected with Matrine injection （50 mg/kg） intraperitoneally since the 7th day after immunization； normal group and model group were given constant volume of normal saline intraperitoneally， once a day， since 18th day after immunization. The neurofunctional score of mice was recorded， and hematoxylin and eosin staining and Luxol fast blue staining were used to observe inflammatory cell infiltration and demyelination in spinal cord tissue. The quantitative reverse transcription PCR and Western blot assay were performed to determine the mRNA expressions of transferrin receptor 1 （TFR1）， nuclear receptor coactivator 4 （NCOA4） and hephaestin （Heph）， and the protein expressions of system Xc

－

（xCT） and glutathione peroxidase 4 （GPx4）.

RESULTS

Compared with normal group， accumulative neurofunctional score was significantly increased in model group （

＜0.01）； inflammatory cell infiltration and demyelination were obvious in spinal cord tissue， and related scores were increased significantly （

＜0.01）. The mRNA expressions of TFR1 and NCOA4 in myelin tissue were up-regulated significantly， while the mRNA expression of Heph and the protein expressions of xCT and GPx4 were down-regulated significantly （

＜0.05 or

＜0.01）. Compared with model group， above indexes of matrine group were all improved significantly （

＜0.05 or

＜0.01）.

CONCLUSIONS

Matrine can improve EAE mice， the mechanism of which may be associated with regulating iron metabolism pathway and xCT/GPx4 pathway in ferroptosis.

关键词

苦参素实验性自身免疫性脑脊髓炎铁代谢胱氨酸-谷氨酸反向转运体/谷胱甘肽过氧化物酶4通路小鼠

Keywords

experimental autoimmune encephalomyelitisiron metabolismxCT/GPx4 pathwaymice

references

JIANG X J，STOCKWELL B R，CONRAD M. Ferroptosis：mechanisms，biology and role in disease[J]. Nat Rev Mol Cell Biol，2021，22（4）：266-282.

JHELUM P，SANTOS-NOGUEIRA E，TEO W，et al. Ferroptosis mediates cuprizone-induced loss of oligodendrocytes and demyelination[J]. J Neurosci，2020，40（48）：9327-9341.

DAVID S，JHELUM P，RYAN F，et al. Dysregulation of iron homeostasis in the central nervous system and the role of ferroptosis in neurodegenerative disorders[J]. Antioxid Redox Signal，2022，37（1/2/3）：150-170.

LI J，CAO F，YIN H L，et al. Ferroptosis：past，present and future[J]. Cell Death Dis，2020，11（2）：88.

HU C L，NYDES M，SHANLEY K L，et al. Reduced expression of the ferroptosis inhibitor glutathione peroxidase-4 in multiple sclerosis and experimental autoimmune encephalomyelitis[J]. J Neurochem，2019，148（3）：426-439.

DOU M M，ZHOU X L，LI L F，et al. Illumination of molecular pathways in multiple sclerosis lesions and the immune mechanism of matrine treatment in EAE，a mouse model of MS[J]. Front Immunol，2021，12：640778.

MA R，CHU Y J，DOU M M，et al. Matrine inhibits the Wnt3a/β-catenin/TCF7L2 signaling pathway in experimental autoimmune encephalomyelitis[J]. J Neuroimmunol，2022，367：577876.

CHU Y J，MA W D，THOME R，et al. Matrine inhibits CNS autoimmunity through an IFN-β-dependent mechanism[J]. Front Immunol，2020，11：569530.

CHU Y J，JING Y L，ZHAO X Y，et al. Modulation of the HMGB1/TLR4/NF-κB signaling pathway in the CNS by matrine in experimental autoimmune encephalomyelitis[J]. J Neuroimmunol，2021，352：577480.

赵培源，陈少昀，刘喜红，等. 多发性硬化实验动物模型的研究与应用进展[J]. 中国实验动物学报，2020，28（3）：405-409.

PARK E，CHUNG S W. ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation[J]. Cell Death Dis，2019，10（11）：822.

FILLEBEEN C，CHARLEBOIS E，WAGNER J，et al. Transferrin receptor 1 controls systemic iron homeostasis by fine-tuning hepcidin expression to hepatocellular iron load[J]. Blood，2019，133（4）：344-355.

米海潮，史敏，崔芳. 铁自噬与铁死亡及其相关疾病[J]. 中国生物化学与分子生物学报，2022，38（9）：1133-1140.

JI C Y，STEIMLE B L，BAILEY D K，et al. The ferroxidase hephaestin but not amyloid precursor protein is required for ferroportin-supported iron efflux in primary hippocampal neurons[J]. Cell Mol Neurobiol，2018，38（4）：941-954.

张亮，廖勇群，夏秦川，等. 铁死亡调控信号通路以及在相关疾病中的研究进展[J]. 中国临床药理学与治疗学，2022，27（2）：227-234.

唐珍，王含彦，郭冬梅. 胱氨酸/谷氨酸反向转运体的研究进展[J]. 川北医学院学报，2021，36（11）：1536-1540.

张新月，刘晨萌，马瑜徽，等. TXNIP/Trx-1/GPX4通路促进新生大鼠缺氧缺血后海马神经元铁死亡的作用机制[J]. 中国当代儿科杂志，2022，24（9）：1053-1060.

STOCKWELL B R，FRIEDMANN ANGELI J P，BAYIR H，et al. Ferroptosis：a regulated cell death nexus linking metabolism，redox biology，and disease[J]. Cell，2017，171（2）：273-285.

SONG X X，ZHU S，CHEN P，et al. AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system xc- activity[J]. Curr Biol，2018，28（15）：2388-2399.e5.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Optimization of extraction process of polysaccharide from Baihe dihuang decoction and study on its anti-anxiety and anti-depression efficacy

Study on improvement effects and mechanism of imperatorin on cachexia model mice

Prevention of renal interstitial fibrosis by osthole in diabetic nephropathy model mice

Effects of the components of traditional Chinese medicine for invigorating qi and activating blood circulation on cognitive function of chronic cerebral ischemia model mice and its mechanism

Effects of Achyranthis bidentatae-Cynanchum otophyllum on oxidative stress of cerebral tissue in Parkinson’s disease mice with syndrome of hyperactivity of liver-Yang

Related Author

TANG Lin

ZHAO Hongqing

YANG Hui

LIU Jian

HE Yiran

LI Li

ZHANG Shuihan

WANG Yaxian

Related Institution

Hospital-made Preparations Center， the First Affiliated Hospital of Hunan University of Chinese Medicine

Science & Technology Innovation Center， Hunan University of Chinese Medicine

Medical Innovation Experiment Center， the First Affiliated Hospital of Hunan University of Chinese Medicine

Dept. of Pharmacy， the First Affiliated Hospital of Hunan University of Chinese Medicine

Hunan Academy of Chinese Medicine

Address：8/F,129 Daping Main Street,Yuzhong District,Chongqing 400042,P.R.China
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰