中国中药杂志

2019, v.44(15) 3330-3334

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雷公藤甲素对脾脏Th17/Treg细胞的影响
Effect of triptolide on Th17/Treg cells in spleen

王欣之;农程;江振洲;张陆勇;
WANG Xin-zhi;NONG Cheng;JIANG Zhen-zhou;ZHANG Lu-yong;Jiangsu Key Laboratory of Drug Screening,China Pharmaceutical University;Key Laboratory of Drug Quality Control and Pharmacovigilance,Ministry of Education,China Pharmaceutical University;Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University;Center for Drug Screening and Pharmacodynamics Evaluation,School of Pharmacy,Guangdong Pharmaceutical University;

摘要(Abstract):

雷公藤甲素(TP)是传统中药雷公藤的主要活性单体,有很强的免疫调节作用。介导炎性反应的Th17细胞和介导免疫耐受的Treg细胞在免疫应答中起着重要的调控作用,前期研究发现,TP能引起肝脏Th17/Treg失衡,而TP对脾脏Th17/Treg细胞的影响未有明确研究,因此该研究考察TP对脾脏Th17/Treg细胞的影响。在体外通过细胞毒性实验检测TP对脾脏淋巴细胞增殖影响,用不同浓度(2. 5,5,20,40 nmol·L~(-1)) TP给予脾脏淋巴细胞后,用微球分析法检测细胞上清分泌的细胞因子,用qRT-PCR法检测细胞因子信号传导抑制蛋白(SOCS)的mRNA表达;在体内给予雌性C57BL/6小鼠500μg·kg-1TP后连续观察24 h,检测TP对脾脏组织结构和Th17/Treg细胞比例的影响。结果显示,TP在体外对脾脏淋巴细胞作用24 h的IC50为19. 6 nmol·L~(-1),2. 5,5 nmol·L~(-1)TP抑制IL-2和IL-10的分泌,诱导SOCS-1和SOCS-3的mRNA表达; 500μg·kg-1TP在体内对小鼠脾脏无明显毒性,在12 h能诱导脾脏Th17细胞比例增加,在12,24 h抑制脾脏Treg细胞比例。综上表明,TP通过SOCS-1/3下调IL-2和IL-10的分泌,增加Th17细胞比例,抑制Treg细胞比例。
Triptolide( TP) is isolated from the traditional Chinese medicine Tripterygium wilfordii,which exhibits notable immuneregulative effect. Th17 cells involve in inflammatory response and Treg cells contribute to immune tolerance. They both play an important role in immune response. Previous studies have investigated that TP induced hepatic Th17/Treg imbalance. However,the effect of TP on spleen Th17/Treg cells remains unclear. Therefore,the aim of present study was to investigate the effect of TP on Th17/Treg cells in spleen. In this study,the effect of TP on the proliferation of splenic lymphocyte was detected by cytotoxicity test in vitro. After different concentrations of TP( 2. 5,5,20,40 nmol·L~(-1)) were given to splenic lymphocyte,cytokines secreted from the supernatant of splenic lymphocyte were detected by cytometric bead array,and the expression of suppressor of cytokine signaling( SOCS) mRNA was detected by qRT-PCR. Female C57 BL/6 mice were continuously observed for 24 h after treatment of 500 μg·kg-1 TP. The effects of TP on the splenic tissue structure and the percentage of Th17/Treg cells were examined. The results showed that the IC50 of TP was19. 6 nmol·L~(-1) in spleen lymphocytes. TP inhibited the secretion of IL-2 and IL-10 and induced the expression of SOCS-1/3 mRNA in spleen lymphocytes at the dosage of 2. 5 and 5 nmol·L~(-1) after 24 h in vitro. Administration of TP at dosage of 500 μg·kg-1 had no significant spleen toxicity in vivo. TP treatment increased the percentage of Th17 cells after 12 h and inhibited the proportion of Treg cells after 12 and 24 h. In conclusion,TP reduced the secretion of IL-2 and IL-10 through SOCS-1/3 signaling pathway,thereby induced the percentage of Th17 cells and inhibited the percentage of Treg cells.

关键词(KeyWords): 雷公藤甲素;Th17细胞;Treg细胞;细胞因子信号传导抑制蛋白;IL-2;IL-10
triptolide;Th17 cells;regulatory T cells;suppressor of cytokine signaling;IL-2;IL-10

Abstract:

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基金项目(Foundation): 国家自然科学基金青年基金项目(81703626);国家自然科学基金面上项目(81773995)

作者(Author): 王欣之;农程;江振洲;张陆勇;
WANG Xin-zhi;NONG Cheng;JIANG Zhen-zhou;ZHANG Lu-yong;Jiangsu Key Laboratory of Drug Screening,China Pharmaceutical University;Key Laboratory of Drug Quality Control and Pharmacovigilance,Ministry of Education,China Pharmaceutical University;Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University;Center for Drug Screening and Pharmacodynamics Evaluation,School of Pharmacy,Guangdong Pharmaceutical University;

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