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基于血清代谢组学研究佛手柑内酯治疗肝纤维化的作用机制

吴辉星 鲁澄宇 张振华 龙昌锐 郭桂芬 王炎玉 陈燕纯 付钜雄 乡世健 周本杰

中国药房2024,Vol.35Issue(13):1570-1575,6.
中国药房2024,Vol.35Issue(13):1570-1575,6.DOI:10.6039/j.issn.1001-0408.2024.13.05

基于血清代谢组学研究佛手柑内酯治疗肝纤维化的作用机制

Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis

吴辉星 1鲁澄宇 1张振华 2龙昌锐 1郭桂芬 3王炎玉 2陈燕纯 2付钜雄 1乡世健 4周本杰4

作者信息

  • 1. 广东医科大学药学院,广东 东莞 523808
  • 2. 中山大学附属第七医院药学部,广东 深圳 518107
  • 3. 惠东县人民医院血液净化中心,广东惠州 513600
  • 4. 中山大学附属第七医院药学部,广东 深圳 518107||深圳市中药活性物质筛选与转化重点实验室,广东深圳 518107
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摘要

Abstract

OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics.METHODS Forty mice were divided into normal control group(0.5%carboxymethyl cellulose sodium solution),model group(0.5%carboxymethyl cellulose sodium solution),and BP low-dose and high-dose groups(50,100 mg/kg),with 10 mice in each group.Except for the normal control group,the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model;they were given relevant medicine/solution intragastrically,once a day,for consecutive 8 weeks.After the last medication,the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum were detected,and liver pathological changes were observed;the expressions of α-smooth muscle actin(α-SMA)and Collagen Ⅰ were detected in liver tissue;the serum of the mice was collected for metabolomics analysis.RESULTS Compared with the model group,serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups(P<0.05),while liver fibrosis was improved significantly.Meanwhile,metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group,of which 18 substances were upregulated and 157 substances were downregulated;the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism,butanoate metabolism,fatty acid synthesis,tyrosine metabolism,β-alanine metabolism,nicotinic acid and nicotinamide metabolism,glutathione metabolism,etc.CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism,butanoate metabolism,glutathione metabolism and so on in rats with liver fibrosis.

关键词

佛手柑内酯/肝纤维化/血清代谢组学/差异代谢物/代谢途径

Key words

bergapten/liver fibrosis/serum metabolomics/differential metabolites/metabolic pathway

分类

医药卫生

引用本文复制引用

吴辉星,鲁澄宇,张振华,龙昌锐,郭桂芬,王炎玉,陈燕纯,付钜雄,乡世健,周本杰..基于血清代谢组学研究佛手柑内酯治疗肝纤维化的作用机制[J].中国药房,2024,35(13):1570-1575,6.

基金项目

国家自然科学基金项目(No.82074078) (No.82074078)

广东基础与应用基础研究基金项目(No.2022A1515220027) (No.2022A1515220027)

深圳市科技计划项目(No.ZDSYS20220606100801003) (No.ZDSYS20220606100801003)

中国药房

OA北大核心CSTPCD

1001-0408

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