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藏红花醛对脂多糖诱导的脓毒症相关肝损伤小鼠模型的作用及其机制

陈意 陈羿帆 杜毅超 谭鹏 李童希 白俊杰 付文广

引用本文:
Citation:

藏红花醛对脂多糖诱导的脓毒症相关肝损伤小鼠模型的作用及其机制

DOI: 10.3969/j.issn.1001-5256.2023.11.019
基金项目: 

‍国家自然科学基金 (82170587)

伦理学声明:本研究方案于2021年11月19日经由西南医科大学实验动物伦理委员会审批,批号:20211119-047,符合实验室动物管理与使用准则。
利益冲突声明:本研究不存在任何利益冲突。
作者贡献声明:‍陈意负责课题设计,资料分析,撰写论文;陈意、陈羿帆参与动物造模及实验;李童希、白俊杰、杜毅超、谭鹏负责数据分析和细胞实验;付文广负责实验设计,拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    ‍付文广, fuwg@swmu.edu.cn (ORCID: 0000-0003-3672-9728)

Effect and mechanism of safranal in a mouse model of sepsis-related liver injury induced by lipopolysaccharide

Research funding: 

‍National Natural Science Foundation of China (82170587)

More Information
    Corresponding author: FU Wenguang, fuwg@swmu.edu.cn (ORCID: 0000-0003-3672-9728)
  • 摘要:   目的  探讨藏红花醛对脂多糖(LPS)诱导的脓毒症相关肝损伤(SRLI)小鼠模型的保护作用及其机制。  方法  采用简单随机分组法将32只实验用C57BL/6雄性小鼠分为对照组、单药组、模型组和治疗组,每组各8只。单药组和治疗组腹腔注射藏红花醛(60 mg/kg)预处理7天,模型组和治疗组腹腔注射LPS(10 mg/kg)诱导急性肝损伤。检测各组小鼠血清ALT、AST活性,HE染色观察肝组织切片标本,免疫组化分析信号通路下游蛋白血红素加氧酶-1(HO-1)的表达差异,TUNEL法分析肝细胞凋亡情况,Western Blot法分析肝组织总蛋白[核因子NF-E2相关因子2(Nrf2)、HO-1]表达差异。采用藏红花醛(100 μmol/L)预处理人类肝细胞系L02细胞,通过LPS 100 ng/mL诱导急性肝细胞损伤,DCFH-DA荧光标记氧自由基。  结果  藏红花醛预处理后,治疗组小鼠ALT、AST明显低于模型组(P值均<0.01),治疗组小鼠肝脏维持了较为完整的假小叶结构且坏死面积更小。治疗组小鼠经藏红花醛+LPS处理后肝组织Nrf2、HO-1表达水平相较于模型组明显升高(P值均<0.001),免疫组化结果显示,藏红花醛预处理增加了HO-1阳性细胞的数量。在LPS诱导的急性肝损伤细胞模型中,治疗组相较于模型组ROS的产生量明显减少。  结论  藏红花醛可通过Nrf-2/HO-1通路介导LPS诱导的小鼠SRLI的保护作用。

     

  • 图  1  小鼠血清中转氨酶水平的差异

    Figure  1.  The differences of transaminase levels in mice serum

    图  2  各组小鼠肝组织HE染色结果比较(×200)

    Figure  2.  The difference of liver tissue after HE staining in each group(×200)

    图  3  各组小鼠肝组织免疫组化检测HO-1蛋白水平比较(×200)

    Figure  3.  The protein levels of HO-1 detected by immunohistochemical staining(×200)

    图  4  各组小鼠肝组织Nrf2和HO-1表达量比较

    注: a,Western Blot检测小鼠肝组织中Nrf2和HO-1的蛋白表达水平;b,Nrf2的相对表达水平;c,HO-1的相对表达水平。

    Figure  4.  The expression levels of Nrf2 and HO-1 in liver tissue of mice in each group

    图  5  TUNEL检测各组小鼠肝组织中细胞凋亡情况(×200)

    Figure  5.  Cell apoptosis in liver tissue of mice were detected by TUNEL assay(×200)

    图  6  各组L02细胞中ROS产生量的比较(×200)

    注: a,对照组;b,单药组;c,模型组;d,治疗组。

    Figure  6.  Comparison of ROS production in L02 cells in each group(×200)

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  • 收稿日期:  2023-02-19
  • 录用日期:  2023-03-18
  • 出版日期:  2023-11-28
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