| 雷公藤多苷片中雷公藤甲素与体外肝毒性相关性研究 |
| 投稿时间：2020-05-20 点此下载全文
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| 引用本文：王曼虹,王雪,颜玉静,黄芝瑛,汪祺,文海若.雷公藤多苷片中雷公藤甲素与体外肝毒性相关性研究[J].中国现代中药,2021,23(8):1344-1351 |
| DOI：10.13313/j.issn.1673-4890.20200520001 |
| 摘要点击次数: 391 |
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| 作者中文名 | 作者英文名 | 单位中文名 | 单位英文名 | E-Mail |
| 王曼虹 |
WANG Man-hong |
中国食品药品检定研究院，北京 100050
中山大学 药学院，广东 广州 510006 |
National Institutes for Food and Drug Control, Beijing 100050, China
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China |
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| 王雪 |
WANG Xue |
中国食品药品检定研究院，北京 100050 |
National Institutes for Food and Drug Control, Beijing 100050, China |
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| 颜玉静 |
YAN Yu-jing |
中国食品药品检定研究院，北京 100050
中山大学 药学院，广东 广州 510006 |
National Institutes for Food and Drug Control, Beijing 100050, China
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China |
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| 黄芝瑛 |
HUANG Zhi-ying |
中山大学 药学院，广东 广州 510006 |
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China |
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| 汪祺 |
WANG Qi |
中国食品药品检定研究院，北京 100050 |
National Institutes for Food and Drug Control, Beijing 100050, China |
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| 文海若 |
WEN Hai-ruo |
中国食品药品检定研究院，北京 100050 |
National Institutes for Food and Drug Control, Beijing 100050, China |
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| 基金项目:国家自然科学基金项目（81503347，81503068）；国家“重大新药创制”科技重大专项（2018ZX09201017） |
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| 中文摘要:目的 采用永生化人肝HepaRG细胞明确雷公藤多苷片制剂（Tripterygium Glycoside Tablets，TPT）中主要成分雷公藤甲素（triptolide，TP）与肝毒性的相关性。方法 HepaRG细胞经不同浓度TP及TPT作用24 h后，采用细胞计数试剂盒法（cell vounting kit-8，CCK-8）分别测定TP和来自不同厂家的TPT对HepaRG细胞存活率的影响；采用流式检测法测定TP及TPT的对细胞凋亡率的影响；收集细胞培养液检测谷草转氨酶（AST）、碱性磷酸酶（ALP）、乳酸脱氢酶（LDH）、肌酸激酶（CK）和谷氨酰转肽酶（GGT）等与肝毒性相关的生化指标，并以实时荧光定量多聚核苷酸链式反应（Real-time PCR）法测定白细胞介素-6（IL-6）、IL-10、肿瘤坏死因子-α（TNF-α）和γ-干扰素（IFN-γ）等细胞因子表达水平。结果 TP的半数抑制浓度（the half maximal inhibitory concentration，IC50）为15.14 nmol·L-1。重点考察不同生产企业间TP含量与毒性差异之间的关联，结果发现，TP含量与细胞毒性、细胞凋亡、ALP、CK、TNF-α和IFN-γ变化直接相关，AST、LDH、TNF-α和IFN-γ是检测TP导致的肝细胞毒性较为灵敏的指标。结论 TP为不同企业TPT制剂中主要肝毒性成分。TPT中其他成分仍存在肝毒性风险，值得进一步研究。 |
| 中文关键词:雷公藤多苷片 雷公藤甲素 肝毒性 细胞凋亡 细胞因子 |
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| Correlation Between Triptolide in Tripterygium Glycoside Tablets and Hepatotoxicity in vitro |
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| Abstract:Objective To study the correlation between hepatotoxicity and triptolide (TP), the main component of Tripterygium Glycoside Tablets (TPT), in immortalized human hepatocyte HepaRG cells.Methods The effects of TP and TPT from different manufacturers on the survival of HepaRG cells were determined using the cell counting kit-8 (CCK-8) after treatment with different concentrations of TP and TPT for 24 h. The effects of TP and TPT on apoptosis of HepaRG cells were detected by flow cytometry. The cell culture solution was collected for measuring the biochemical indicators related to hepatotoxicity including aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), and glutamyl transpeptidase (GGT). The expression levels of such cytokines as interleukin-6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α), and γ-interferon (IFN-γ) were assayed by real-time quantitative polymerase chain reaction (Real-time PCR).Results The half maximal inhibitory concentration (IC50) of TP was 15.14 nmol·L-1. The investigation on the correlation between the content of TP from different manufacturers and toxicity revealed that the content of TP was directly correlated with the changes in cytotoxicity, apoptosis, ALP, CK, TNF-α, and IFN-γ. Among them, AST, LDH, TNF-α, and IFN-γ were sensitive indicators for the detection of TP-induced hepatotoxicity.Conclusion TP is the main component that causes hepatotoxicity in TPT from different manufacturers. In addition, other components in TPT may also induce the hepatotoxicity, which deserves to be further studied. |
| keywords:Tripterygium Glycoside Tablets triptolide hepatotoxicity apoptosis cytokines |
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