黄芪甲苷通过PPARγ抑制Th1、Th17分化改善自身免疫性脑脊髓炎

被引：22

作者：

梁莉 ^{[1
]}

鲁佑瑜 ^{[1
]}

劳小平 ^{[2
]}

张兆 ^{[3
]}

林椿人 ^{[4
]}

张炜志 ^{[4
]}

机构：

[1] 上海市第一人民医院嘉定分院上海市嘉定区江桥医院神经内科

[2] 广西医科大学第九附属医院北海市人民医院神经内科

[3] 广西南宁市第一人民医院神经内科

[4] 广西医科大学第十附属医院钦州市第一人民医院神经内科

来源：

免疫学杂志 | 2021年 / 37卷 / 11期

关键词：

黄芪甲苷; 小鼠实验性自身免疫性脑脊髓炎; CD4+T细胞; PPARγ; Th1/Th17分化;

D O I：

暂无

中图分类号：

R285.5 [中药实验药理];

学科分类号：

100806 [中药药理学];

摘要：

目的探讨黄芪甲苷实验性自身免疫性脑脊髓炎（EAE）治疗作用及其机制。方法采用髓磷脂少突胶质细胞糖蛋白35-55(MOG35-55)免疫C57BL/6小鼠构建EAE模型,随机分为对照（PBS）组与黄芪甲苷（AS-IV）组（100 mg/kg）。免疫前3天连续腹腔注射黄芪甲苷,免疫后隔天注射,持续观察小鼠发病情况。取脊髓切片HE染色观察炎性细胞浸润,LFB染色评估脊髓髓鞘脱失,流式细胞数检测CD4+T细胞向Th1与Th17细胞分化比例。提取正常小鼠脾脏中CD4+T细胞,在细胞因子作用下诱导分化,加入不同剂量黄芪甲苷与PPARγ抑制剂T0070907探究其对CD4+T细胞分化的影响。采用Western blot检测PPARγ、NF-κB与NLRP3表达。结果与对照组相比,AS-IV组EAE小鼠发病率降低,发病时间延迟,且骨髓炎性细胞浸润减少,髓鞘脱失抑制,脾脏与脊髓中Th1与Th17细胞表型的含量减少。体外实验中,黄芪甲苷剂量依赖性减少了CD4+T细胞向Th1与Th17细胞表型分化,然而,T0070907逆转了黄芪甲苷的抑制作用。与此同时,无论是在体内还是体外实验中,黄芪甲苷有效增加了PPARγ表达,减少了p-NF-κB与NLRP3表达水平。结论黄芪甲苷通过激活PPARγ,介导NF-κB信号通路抑制,减少CD4+T细胞向Th1与Th17细胞分化,减轻小鼠EAE症状。

引用

收藏

页码：954 / 961

页数：8

相关论文

共 17 条

[1]

The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis [J].

Brambilla, Roberta .

ACTA NEUROPATHOLOGICA, 2019, 137 (05) :757-783

[2]

Boosting phagocytosis and anti-inflammatory phenotype in microglia mediates neuroprotection by PPARγ agonist MDG548 in Parkinson's disease models [J].

Lecca, Daniela ;

Janda, Elzbieta ;

Mulas, Giovanna ;

Diana, Andrea ;

Martino, Concetta ;

Angius, Fabrizio ;

Spolitu, Stefano ;

Casu, Maria Antonietta ;

Simbula, Gabriella ;

Boi, Laura ;

Batetta, Barbara ;

Spiga, Saturnino ;

Carta, Anna R. .

BRITISH JOURNAL OF PHARMACOLOGY, 2018, 175 (16) :3298-3314

[3]

Astragaloside IV attenuates orbital inflammation in Graves' orbitopathy through suppression of autophagy [J].

Li, Hong ;

Zhang, Yali ;

Min, Jie ;

Gao, Long ;

Zhang, Ren ;

Yang, Yucheng .

INFLAMMATION RESEARCH, 2018, 67 (02) :117-127

[4]

GPR65 inhibits experimental autoimmune encephalomyelitis through CD4+ T cell independent mechanisms that include effects on iNKT cells [J].

Wirasinha, Rushika C. ;

Vijayan, Dipti ;

Smith, Nicola J. ;

Parnell, Grant P. ;

Swarbrick, Alexander ;

Brink, Robert ;

King, Cecile ;

Stewart, Graeme ;

Booth, David R. ;

Batten, Marcel .

IMMUNOLOGY AND CELL BIOLOGY, 2018, 96 (02) :128-136

[5]

Absence of Notch1 in murine myeloid cells attenuates the development of experimental autoimmune encephalomyelitis by affecting Th1 and Th17 priming [J].

Fernandez, Miriam ;

Monsalve, Eva M. ;

Lopez-Lopez, Susana ;

Ruiz-Garcia, Almudena ;

Mellado, Susana ;

Caminos, Elena ;

Javier Garcia-Ramirez, Jose ;

Laborda, Jorge ;

Tranque, Pedro ;

Diaz-Guerra, Maria Jose M. .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2017, 47 (12) :2090-2100

[6]

Physical Exercise Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Peripheral Immune Response and Blood-Brain Barrier Disruption [J].

Souza, Priscila S. ;

Goncalves, Elaine D. ;

Pedroso, Giulia S. ;

Farias, Hemelin R. ;

Junqueira, Stella C. ;

Marcon, Rodrigo ;

Tuon, Talita ;

Cola, Maira ;

Silveira, Paulo C. L. ;

Santos, Adair R. ;

Calixto, Joao B. ;

Souza, Claudio T. ;

de Pinho, Ricardo A. ;

Dutra, Rafael C. .

MOLECULAR NEUROBIOLOGY, 2017, 54 (06) :4723-4737

[7]

Research review on the pharmacological effects of astragaloside IV [J].

Li, Lei ;

Hou, Xiaojiao ;

Xu, Rongfang ;

Liu, Chang ;

Tu, Menbayaer .

FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2017, 31 (01) :17-36

[8]

MALT1 inhibitors prevent the development of DSS-induced experimental colitis in mice via inhibiting NF-κB and NLRP3 inflammasome activation [J].

Liu, Wen ;

Guo, Wenjie ;

Hang, Nan ;

Yang, Yuanyuan ;

Wu, Xuefeng ;

Shen, Yan ;

Cao, Jingsong ;

Sun, Yang ;

Xu, Qiang .

ONCOTARGET, 2016, 7 (21) :30536-30549

[9]

Inhibition of Interferon Regulatory Factor 4 Suppresses Th1 and Th17 Cell Differentiation and Ameliorates Experimental Autoimmune Encephalomyelitis [J].

Yang, C. ;

He, D. ;

Yin, C. ;

Tan, J. .

SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2015, 82 (04) :345-351

[10]

Th1 and Th17 Cytokines Drive Inflammation in Takayasu Arteritis [J].

Saadoun, D. ;

Garrido, M. ;

Comarmond, C. ;

Desbois, A. C. ;

Domont, F. ;

Savey, L. ;

Terrier, B. ;

Geri, G. ;

Rosenzwajg, M. ;

Klatzmann, D. ;

Fourret, P. ;

Cluzel, P. ;

Chiche, L. ;

Gaudric, J. ;

Koskas, F. ;

Cacoub, P. .

ARTHRITIS & RHEUMATOLOGY, 2015, 67 (05) :1353-1360