补骨脂素对四氯化碳致小鼠急性肝损伤的改善作用

张艳; 江振洲; 张陆勇

doi:10.11665/j.issn.1000-5048.20210512

补骨脂素对四氯化碳致小鼠急性肝损伤的改善作用

1.
中国药科大学药物科学研究院新药筛选中心，南京 210009
2.
广东药科大学新药研发中心，广州 510006

基金项目: 公益性行业科研专项资助项目（No.201507004-002）；重大新药创制国家科技重大专项资助项目（No.2015ZX09501004-002-004）

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- 收稿日期: 2021-03-01
- 修回日期: 2021-09-16
- 刊出日期: 2021-10-24

Ameliorative effect of psoralen on acute liver injury induced by carbon tetrachloride in mice

1.
New Drug Screening Center, Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing 210009
2.
Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China

Funds: This study was supported by the Non-profit Industry Scientific Research Project (No.201507004-002) and China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs (No.2015ZX09501004-002-004)

摘要

摘要: 研究补骨脂素（psoralen，PSO）对四氯化碳（CCl₄）致小鼠急性肝损伤的改善作用及其机制。雌性C57BL/6J小鼠连续灌胃补骨脂素或阳性对照药烯丙基化硫（DAS） 4 d，第4天腹腔注射CCl₄，建立CCl₄致急性肝损伤小鼠模型。检测血清生化指标丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平；HE染色观察肝脏病理学变化；Western blot检测细胞色素P450 2E1（CYP2E1）的蛋白水平；免疫组织化学染色（IHC）检测CYP2E1的蛋白水平；RT-PCR检测CYP2E1以及炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6 （IL-6）的基因水平。与模型组相比，补骨脂素能够改善CCl₄引起的炎性细胞浸润以及肝细胞坏死情况，显著降低血清ALT、AST水平，下调炎症因子TNF-α和IL-6的水平，抑制CYP2E1的蛋白表达。结果表明，补骨脂素对CCl₄致小鼠急性肝损伤具有改善作用，其机制可能是通过抑制CYP2E1的蛋白表达发挥药效作用。
- 补骨脂素 /
- 四氯化碳 /
- 急性肝损伤 /
- 细胞色素P450 2E1
Abstract: To investigate the ameliorative effect of psoralen (PSO) on carbon tetrachloride (CCl₄)-induced acute liver injury in mice and its potential mechanism, female C57BL/6J mice aged 6-8 weeks were continuously administrated with psoralen or positive control drug diallyl sulfide (DAS) intragastrically for 4 days.On day 4, except that the control group were treated with vehicle control, other groups were all given carbon tetrachloride intraperitoneally to establish a carbon tetrachloride acute liver injury model.Serum biochemical indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected; liver pathological changes were observed by HE staining; cytochrome P450 2E1 (CYP2E1) protein levels were detected by Western blot; the protein level of CYP2E1 were detected by immunohistochemistry (IHC) staining; and the gene levels of CYP2E1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by RT-PCR.Compared with the model group, psoralen could improve the inflammatory cell infiltration and hepatocyte necrosis caused by carbon tetrachloride, significantly reducing the serum ALT and AST levels, down-regulating the inflammatory factors TNF-α and IL-6 levels, and inhibiting CYP2E1 protein expression.The results show that psoralen can ameliorate the acute liver injury induced by carbon tetrachloride in mice, with the possible mechanism inhibiting the protein expression of CYP2E1.
- psoralen /
- carbon tetrachloride /
- acute liver injury /
- cytochrome P450 2E1

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参考文献(22)

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补骨脂素对四氯化碳致小鼠急性肝损伤的改善作用

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出版历程

Ameliorative effect of psoralen on acute liver injury induced by carbon tetrachloride in mice

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