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蟾酥及其潜在代用品NJ2196抗LPS诱导小鼠神经炎症的等效性评价

钱意 张亚文 吕翔 朱雨雨 李念光 段金廒 周婧 马宏跃

钱意, 张亚文, 吕翔, 朱雨雨, 李念光, 段金廒, 周婧, 马宏跃. 蟾酥及其潜在代用品NJ2196抗LPS诱导小鼠神经炎症的等效性评价[J]. 南京中医药大学学报, 2022, 38(10): 915-920. doi: 10.14148/j.issn.1672-0482.2022.0915
引用本文: 钱意, 张亚文, 吕翔, 朱雨雨, 李念光, 段金廒, 周婧, 马宏跃. 蟾酥及其潜在代用品NJ2196抗LPS诱导小鼠神经炎症的等效性评价[J]. 南京中医药大学学报, 2022, 38(10): 915-920. doi: 10.14148/j.issn.1672-0482.2022.0915
QIAN Yi, ZHANG Ya-wen, LYU Xiang, ZHU Yu-yu, LI Nian-guang, DUAN Jin-ao, ZHOU Jing, MA Hong-yue. Equivalence Evaluation of Venenum Bufonis and Its Potential Substitute NJ2196 against LPS-Induced Neuroinflammation in Mice[J]. Journal of Nanjing University of traditional Chinese Medicine, 2022, 38(10): 915-920. doi: 10.14148/j.issn.1672-0482.2022.0915
Citation: QIAN Yi, ZHANG Ya-wen, LYU Xiang, ZHU Yu-yu, LI Nian-guang, DUAN Jin-ao, ZHOU Jing, MA Hong-yue. Equivalence Evaluation of Venenum Bufonis and Its Potential Substitute NJ2196 against LPS-Induced Neuroinflammation in Mice[J]. Journal of Nanjing University of traditional Chinese Medicine, 2022, 38(10): 915-920. doi: 10.14148/j.issn.1672-0482.2022.0915

蟾酥及其潜在代用品NJ2196抗LPS诱导小鼠神经炎症的等效性评价

doi: 10.14148/j.issn.1672-0482.2022.0915
基金项目: 

国家自然科学基金面上项目 82073975

国家自然科学基金面上项目 81673563

国家自然科学基金面上项目 81102762

国家自然科学基金面上项目 3901894

江苏省方剂高技术研究重点实验室/江苏省中药资源产业化过程协同创新中心项目 ZDXM-2022-02

江苏省方剂高技术研究重点实验室/江苏省中药资源产业化过程协同创新中心项目 ZDXM-14

江苏省青蓝工程学术带头人项目 

详细信息
    作者简介:

    钱意, 女, 硕士研究生, E-mail: qianyi_nj@126.com

    马宏跃, 教授,博士生导师,主要从事中药动物药蟾酥研究,采用化学蛋白质组学技术为先导,开展其活性物质基础、药效与安全性和资源代用研究。先后主持国家自然科学基金4项、教育部霍英东基金等部省级项目6项、江苏省哲学社科基金1项。在Acta Pharmaceutica Sinica B、Anal Chim Actav Talanta、Signal Transduct Target Ther. Proteomics. Biomed Pharmacother、Front Pharmacol等SCI期刊上发表学术论文80佘篇授权中国专利10项。入选江苏省333、六大人才和青蓝工程学术带头人培养对象。第三届江苏省中医药十佳青年之星、全国大学生“挑战杯”科创二等奖指导老师、江苏省优秀毕业设计团队奖指导老师等荣誉称号

    通讯作者:

    周婧, 女, 副教授, 主要从事中药资源与鉴定的研究, E-mail: zhoujing_nj@126.com

    马宏跃, 男, 教授, 主要从事蟾酥活性物质基础和安全性研究, E-mail: hongyuema@njucm.edu.cn

  • 中图分类号: R285.5

Equivalence Evaluation of Venenum Bufonis and Its Potential Substitute NJ2196 against LPS-Induced Neuroinflammation in Mice

  • 摘要:   目的  评价蟾酥及其潜在代用品NJ2196抗脂多糖(LPS)诱导小鼠神经炎症的等效性。  方法  63只SPF级雄性ICR小鼠随机分为对照组、模型组、氟西汀组、蟾酥低剂量组、蟾酥高剂量组、NJ2196低剂量组、NJ2196高剂量组, 每组9只。除对照组外, 每组单次给予LPS(0.83 mg · kg-1, 腹腔注射)建立炎性抑郁模型。氟西汀组、蟾酥低剂量组、蟾酥高剂量组、NJ2196低剂量组、NJ2196高剂量组分别灌胃氟西汀30 mg · kg-1, 蟾酥30 mg · kg-1, 蟾酥90 mg · kg-1, NJ2196 30 mg · kg-1, NJ2196 90 mg · kg-1, 对照组和模型组给予等量生理盐水。观察小鼠悬尾累积不动时间和强迫游泳累积不动时间; ELISA法检测小鼠血清炎症因子白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α水平; qPCR法检测海马组织炎症因子IL-6和TNF-α以及脑源性神经营养因子(BDNF) mRNA表达水平; 高灵敏度脂质组学分析蟾酥和NJ2196对炎性类花生酸的影响。  结果  与模型组相比, 蟾酥和NJ2196能够显著降低小鼠悬尾累积不动时间(P < 0.01)和强迫游泳累积不动时间(P < 0.01), 显著降低小鼠血清中炎症因子IL-1β、TNF-α水平(P < 0.01), 显著降低小鼠海马体中炎症因子IL-6、TNF-α mRNA表达水平(P < 0.01)以及BDNF mRNA表达水平(P < 0.01), 高灵敏度脂质组学分析显示, 炎症因子的变化可能与来自环氧合酶(COX)途径的炎症介质的下调有关。各剂量蟾酥与NJ2196比较无显著性差异(P>0.05)。  结论  蟾酥及其潜在代用品NJ2196具有显著的抗炎性抑郁活性, 在LPS诱导小鼠神经炎症模型上两者具有一定等效性。

     

  • 图  1  蟾酥和NJ2196对小鼠抑郁行为的影响

    注: 与对照组比较, ##P < 0.01;与模型组比较, **P < 0.01。x±s, n=9。

    Figure  1.  Effects of Chansu and NJ2196 on depressive behavior in mice

    图  2  蟾酥和NJ2196对小鼠血清炎症因子水平的影响

    注: 与对照组比较, ##P < 0.01;与模型组比较, **P < 0.01。x±s, n=6。

    Figure  2.  Effect of Chansu and NJ2196 on serum inflammatory factor levels in mice

    图  3  蟾酥和NJ2196对小鼠海马组织炎症因子mRNA表达的影响

    注: 与对照组比较, #P < 0.05,##P < 0.01;与模型组比较, **P < 0.01。x±s, n=5。

    Figure  3.  Effects of Chansu and NJ2196 on mRNA expression of inflammatory factors in mouse hippocampal tissue

    图  4  蟾酥和NJ2196对小鼠海马组织BDNF mRNA表达的影响

    注: 与模型组比较, *P < 0.05, **P < 0.01。x±s, n=5。

    Figure  4.  Effect of Chansu and NJ2196 on BDNF mRNA expression in mouse hippocampal tissue

    图  5  蟾酥和NJ2196对脑组织COX途径中炎症介质的影响

    注: 与对照组比较, ##P < 0.01;与模型组比较, *P < 0.05, **P < 0.01。x±s, n=5。

    Figure  5.  Effect of Chansu and NJ2196 on inflammatory mediators in the COX pathway of brain tissue

    表  1  引物序列

    Table  1.   Primer sequences

    基因 上游引物(5'→3') 下游引物(5'→3')
    GAPDH ACCCCAGCAAGGACACTGAGCAAG GGCCCCTCCTGTTAT TATGGGGGT
    IL-6 AGACAAAGCCAGAGTCCTTCAGAGA GCCACTCCTTCTGTGACTCCAGC
    TNF-α CCCTCCTGGCCAACGGCATG TCGGGGCAGCCT TGTCCCTT
    BDNF AGGTCTGACGACGACATCACT CTTCGTTGGGCCGAACCTT
    下载: 导出CSV
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  • 收稿日期:  2022-08-20
  • 网络出版日期:  2022-10-25
  • 发布日期:  2022-10-10

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