• CA
  • JST
  • FSTA
  • SCOPUS
  • 北大核心期刊
  • 中国科技核心期刊CSTPCD
  • 中国精品科技期刊
  • RCCSE中国核心学术期刊
  • 中国农业核心期刊
  • 中国生物医学文献服务系统SinoMed收录期刊

甘草葛根发酵组合物对慢性肝损伤大鼠的保护作用

王静 李凤娟 张化朋 刘敬兰 吴力克

王静,李凤娟,张化朋,等. 甘草葛根发酵组合物对慢性肝损伤大鼠的保护作用[J]. 食品工业科技,2022,43(12):369−376. doi:  10.13386/j.issn1002-0306.2021110140
引用本文: 王静,李凤娟,张化朋,等. 甘草葛根发酵组合物对慢性肝损伤大鼠的保护作用[J]. 食品工业科技,2022,43(12):369−376. doi:  10.13386/j.issn1002-0306.2021110140
WANG Jing, LI Fengjuan, ZHANG Huapeng, et al. Study on Protective Effects of Glycyrrhiza and Pueraria Fermentation Composition on Rats with Chronic Liver Injury[J]. Science and Technology of Food Industry, 2022, 43(12): 369−376. (in Chinese with English abstract). doi:  10.13386/j.issn1002-0306.2021110140
Citation: WANG Jing, LI Fengjuan, ZHANG Huapeng, et al. Study on Protective Effects of Glycyrrhiza and Pueraria Fermentation Composition on Rats with Chronic Liver Injury[J]. Science and Technology of Food Industry, 2022, 43(12): 369−376. (in Chinese with English abstract). doi:  10.13386/j.issn1002-0306.2021110140

甘草葛根发酵组合物对慢性肝损伤大鼠的保护作用

doi: 10.13386/j.issn1002-0306.2021110140
基金项目: 山东省重大科技创新工程项目(2019JZZY020908):中药护肝新药GSY-1炮制工艺质量控制技术研究及制剂研制。
详细信息
    作者简介:

    王静(1981−),女,硕士,副研究员,研究方向:功能益生菌菌种选育与功能微生态制剂的研究与开发,E-mail:nihaomarine@126.com

    通讯作者:

    吴力克(1956−),男,硕士,教授,研究方向:感染病学及微生态学,E-mail:58679826@qq.com

  • 中图分类号: R363

Study on Protective Effects of Glycyrrhiza and Pueraria Fermentation Composition on Rats with Chronic Liver Injury

  • 摘要: 目的:研究甘草葛根发酵组合物对四氯化碳(CCl4)致慢性肝损伤大鼠的保护作用及潜在作用机制。方法:采用SD大鼠分别灌胃生理盐水、甘利欣甘草酸二铵胶囊(GLX)、甘草葛根发酵组合物,通过四氯化碳处理建立大鼠慢性肝损伤模型。采用酶联免疫吸附法检测小鼠血清中肝功能指标(ALT、AST、TBIL、TP)、肝纤指标(PLD、TGF-β、HA)、内毒素(LPS)和炎症因子(TNF-α、IL-6)的含量;通过光镜和透射电镜观察小鼠肝组织病理性改变;同时,对不同处理组进行肠道菌群的定量分析。结果:与生理盐水处理组比较,甘草葛根发酵组合物处理组小鼠血清中AST、ALT水平极显著降低(P<0.01);甘草葛根发酵组合物处理组造模前后血清中TBIL、TP水平无明显差异;肝纤维化指标结果显示,甘草葛根发酵组合物保护组TGF-β1P<0.01)、PLD(P<0.01)、HA(P<0.05)指标显著低于生理盐水处理对照组;与生理盐水处理对照组比较,甘草葛根发酵组合物处理组造模前后血清IL-6、LPS水平差异不显著,甘草葛根发酵组合物处理组极显著降低TNF-α水平(P<0.01);病理观察显示,甘草葛根发酵组合物和GLX处理组肝组织未出现明显的病理性改变;菌群分析显示,甘草葛根发酵组合物保护组EMB、EC、KV、CD数量降低,TPY、MRS增高;结论:甘草葛根发酵组合物和GLX对CCl4所致大鼠慢性肝损伤具有一定的保护作用,其中甘草葛根发酵组合物在抗慢性肝损伤过程中的肝纤维化、降低炎症和内毒素水平以及调节肠道菌群方面具有更显著的作用。
  • 图  1  不同处理组经CCl4造模后的体重变化情况

    Figure  1.  Changes in body weight of different treatment groups after CCl4 modeling

    图  2  CCl4造模前后不同处理组肝功能指标

    Figure  2.  Liver function indexes of different treatment groups before and after CCl4 modeling

    注:组间造模前与造模后相比:P<0.05,※※P<0.01;保护组造模后与生理盐水组造模后相比:P<0.05,▼▼P<0.01;图3~图4同。

    图  3  CCl4造模前后不同处理组肝纤维化指标

    Figure  3.  Liver fibrosis indexes of different treatment groups before and after CCl4 modeling

    图  4  CCl4造模前后不同处理组内毒素、细胞因子指标

    Figure  4.  Liver endotoxin and cytokine indexes of different treatment groups before and after CCl4 modeling

    图  5  不同组大鼠慢性肝损伤肝脏病理图

    Figure  5.  Liver pathology of chronic liver injury in different groups of rats

    注:从左到右,NS未保护、GLX保护组、GCQ保护组,12周。

    图  6  不同组慢性肝损伤大鼠光镜观察肝脏病理图(100×)

    Figure  6.  Light microscope observation of liver pathology in different groups of rats with chronic liver injury (100×)

    注:从左到右,NS未保护组、GLX保护组、GCQ保护组,12周。

    图  7  不同组慢性肝损伤大鼠电镜观察肝脏病理图(10000×)

    Figure  7.  Electron microscopic observation of liver pathology in different groups of rats with chronic liver injury (10000×)

    注:从左到右,NS未保护组、GLX保护组、GCQ保护组,12周;A-细胞外基质中大量胶原原纤维;B-线粒体变性,大小及形态不一,基质致密,基质颗粒增大;C-光面内质网增生并囊泡化。

    图  8  不同处理组慢性肝损伤大鼠肠道菌群示意图

    Figure  8.  Schematic diagram of intestinal flora of rats with chronic liver injury in different treatment groups

  • [1] 李冀, 李想, 曹明明, 等. 甘草药理作用及药对配伍比例研究进展[J]. 上海中医药杂志,2019,53(7):83−87. [LI Ji, LI Xiang, CAO Mingming, et al. Research progress in pharmacological actions of liquorice and proportion of couplet medicines in combination[J]. Shanghai Journal of Traditional Chinese Medicine,2019,53(7):83−87.

    LI Ji, LI Xiang, CAO Mingming, et al. Research progress in pharmacological actions of liquorice and proportion of couplet medicines in combination[J]. Shanghai Journal of Traditional Chinese Medicine, 2019, 53(7): 83-87.
    [2] 甘草酸制剂肝病临床应用专家共识[J]. 临床肝胆病杂志, 2016, 32(5): 844−852.

    Expert consensus on clinical application of glycyrrhizin preparation in the treatment of liver diseases[J]. J Clin Hepatol, 2016, 32(5): 844−852.
    [3] 史晨旭, 杜佳蓉, 吴威, 等. 葛根化学成分及药理作用研究进展[J]. 中国现代中药,2021,23(12):2177−2195. [SHI Chenxu, DU Jiarong, WU Wei, et al. Advances in the study of chemical constituents and pharmacological action of Puerariae lobatae radix[J]. Modern Chinese Medicine,2021,23(12):2177−2195.

    SHI Chenxu, DU Jiarong, WU Wei, et al. Advances in the study of chemical constituents and pharmacological action of Puerariae lobatae radix[J]. Modern Chinese Medicine, 2021, 23(12): 2177-2195.
    [4] 木盼盼, 安琪, 张彦昭, 等. 一测多评法测定葛根药材中9个异黄酮成分的含量[J]. 中国中药杂志,2019,44(22):4888−4895. [MU Panpan, AN Qi, ZHANG Yanzhao, et al. Determination of 9 isoflavonoids in Puerariae lobatae radix with quantitative analysis of multi-components by single marker[J]. China Journal of Chinese Materia Medica,2019,44(22):4888−4895.

    MU Panpan, AN Qi, ZHANG Yanzhao, et al. Determination of 9 isoflavonoids in Puerariae lobatae radix with quantitative analysis of multi-components by single marker[J]. China Journal of Chinese Materia Medica, 2019, 44(22) : 4888-4895.
    [5] 赵月蓉, 侯碧玉, 张莉, 等. 葛根素对实验性肝损伤的治疗作用研究进展[J]. 中国新药杂志,2017,26(9):1005−1010. [ZHAO Yuerong, HOU Biyu, ZHANG Li, et al. Research progress of puerarin in the treatment of experimental liver injury[J]. Chinese Journal of New Drugs,2017,26(9):1005−1010.

    ZHAO Yuerong, HOU Biyu, ZHANG Li, et al. Research progress of puerarin in the treatment of experimental liver injury[J]. Chinese Journal of New Drugs, 2017, 26(9): 1005-1010.
    [6] 朱振元, 罗游, 薛婧, 等. 葛根功能饮料的急性毒性及解酒护肝功效评价[J]. 食品研究与开发,2016,37(21):160−163. [ZHU Zhenyuan, LUO You, XUE Jing, et al. Acute toxicity test and sober and hepatoproctive efficacy evaluation of radix puerariae functional beverage[J]. Food Research and Development,2016,37(21):160−163. doi:  10.3969/j.issn.1005-6521.2016.21.037

    ZHU Zhenyuan, LUO You, XUE Jing, et al. Acute toxicity test and sober and hepatoproctive efficacy evaluation of radix puerariae functional beverage[J]. Food Research and Development, 2016, 37(21): 160-163. doi:  10.3969/j.issn.1005-6521.2016.21.037
    [7] KAI M C, STEFANIE A, CHRISTIAN T. Role of bile acids in the gut-liver axis[J]. Journal of Hepatology,2018,68(5):1083−1085. doi:  10.1016/j.jhep.2017.11.025
    [8] WANG Rui, TANG Ruqi, LI Bo, et al. Gut microbiome, liver immunology, and liver diseases[J]. Cellular & Molecular Immunology,2021(8):4−17.
    [9] ANUPRIYA T, JUSTINE D, DAVID A B, et al. The gut-liver axis and the intersection with the microbiome[J]. Nature Reviews Gastroenterology & Hepatology,2018,15:397−411.
    [10] SIDDHARTHA S G, WANG J, PAUL J Y, et al. Intestinal barrier function and metabolic/liver diseases[J]. Liver Research,2020(4):81−87.
    [11] RYO A. Commensal microbe-derived acetate suppresses NAFLD/NASH development via hepatic FFAR2 signalling in mice[J]. Microbiome,2021,9(1):188. doi:  10.1186/s40168-021-01125-7
    [12] SHARPTON S, SCHNABL B, KNIGHT R, et al. Current concepts, opportunities and challenges of gut microbiome-based personalized medicine in nonalcoholic fatty liver disease[J]. Cell Metabolism,2011,33(1):21−32.
    [13] 孟凡涛, 刘冬菊. 研究中药发酵炮制法[J]. 世界最新医学信息文摘,2018,18(10):8−9. [MENG Fantao, LIU Dongju. To study the method of fermentation of Chinese medicine[J]. World Latest Medicine Informationn (Electronic Version),2018,18(10):8−9.

    MENG Fantao, LIU Dongju. To study the method of fermentation of Chinese medicine[J]. World Latest Medicine Informationn (Electronic Version), 2018, 18(10): 8-9.
    [14] 李艳凤, 翟梦颖, 李雨昕, 王等. 发酵法在中药研究中的应用[J]. 医学综述,2020,26(4):753−757. [LI Yanfeng, ZHAI Mengying, LI Yuxin, et al. Application of fermentation method in study of traditional Chinese medicine[J]. Medical Recapitulate,2020,26(4):753−757. doi:  10.3969/j.issn.1006-2084.2020.04.025

    LI Yanfeng, ZHAI Mengying, LI Yuxin, et al. Application of fermentation method in study of traditional Chinese medicine[J]. Medical Recapitulate, 2020, 26(4): 753-757. doi:  10.3969/j.issn.1006-2084.2020.04.025
    [15] 张丽霞, 高文远, 王海洋. 微生物技术在中药炮制中的应用[J]. 中国中药杂志,2012,37(24):3695−3699. [ZHANG Lixia, GAO Wenyuan, WANG Haiyang. Application of microbial technology in the processing of traditional[J]. Chinese Medicine China Journal of Chinese Materia Medica,2012,37(24):3695−3699.

    ZHANG Lixia, GAO Wenyuan, WANG Haiyang. Application of microbial technology in the processing of traditional[J]. Chinese Medicine China Journal of Chinese Materia Medica, 2012, 37(24): 3695-3699.
    [16] 彭静, 陈曦. 滨蒿内酯对四氯化碳致小鼠急性肝损伤的保护作用研究[J]. 中国药房,2021,32(2):231−235. [PENG Jing, CHEN Xi. Study on protective effects of scoparone on acute liver injury induced by CCl4 in mice[J]. China Pharmacy,2021,32(2):231−235. doi:  10.6039/j.issn.1001-0408.2021.02.18

    PENG Jing, CHEN Xi. Study on protective effects of scoparone on acute liver injury induced by CCl4 in mice[J]. China Pharmacy, 2021, 32(2): 231-235. doi:  10.6039/j.issn.1001-0408.2021.02.18
    [17] 王昱. 红腹锦鸡肝脏结构的透射电镜观察[J]. 甘肃农业大学学报,2011,4:43−46. [WANG Yu. Transmission electron microscopical observation on the liver structure of Chroysolophus pictus[J]. Journal of Gansu Agricultural University,2011,4:43−46. doi:  10.3969/j.issn.1003-4315.2011.03.009

    WANG Yu. Transmission electron microscopical observation on the liver structure of Chroysolophus pictus[J]. Journal of Gansu Agricultural University, 2011, 4: 43-46. doi:  10.3969/j.issn.1003-4315.2011.03.009
    [18] 刘旭凌, 杨广越, 张玮, 等. 桃红四物汤对CCl4诱导肝纤维化小鼠模型的干预作用及其机制[J]. 临床肝胆病杂志,2021,37(11):2563−2568. [LIU Xuling, YANG Guangyue, ZHANG Wei, et al. Therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism[J]. J Clin Hepatol,2021,37(11):2563−2568. doi:  10.3969/j.issn.1001-5256.2021.11.016

    LIU Xuling, YANG Guangyue, ZHANG Wei, et al. Therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism[J]. J Clin Hepatol, 2021, 37(11). doi:  10.3969/j.issn.1001-5256.2021.11.016
    [19] 张燕, 范晓翔, 章美武, 等. NLRC5 调节转化生长因子-β1诱导的肝星状细胞活化及逆转对肝纤维化的影响[J]. 中国全科医学,2020,23(24):3051−3059. [ZHANG Yan, FAN Xiaoxiang, ZHANG Meiwu, et al. Role of NLRC5 in the activation of hepatic stellate cells induced by TGF-β1 and reversal of hepatic fibrosis[J]. Chinese General Practice,2020,23(24):3051−3059.

    ZHANG Yan, FAN Xiaoxiang, ZHANG Meiwu, et al. Role of NLRC5 in the activation of hepatic stellate cells induced by TGF-β1 and reversal of hepatic fibrosis[J]. Chinese General Practice, 2020, 23(24): 3051-3059.
    [20] 张永超, 毕研贞, 方萧, 等. 益生菌对慢加急性肝衰竭大鼠模型的保护作用及其机制[J]. 临床肝胆病杂志,2019,35(7):1570−1575. [ZHANG Yongchao, BI Yanzhen, FANG Xiao, et al. Protective effect of probiotics in rats with acute-on-chronic liver failure and related mechanism[J]. J Clin Hepatol,2019,35(7):1570−1575. doi:  10.3969/j.issn.1001-5256.2019.07.029

    ZHANG Yongchao, BI Yanzhen, FANG Xiao, et al. Protective effect of probiotics in rats with acute-on-chronic liver failure and related mechanism[J]. J Clin Hepatol, 2019, 35(7): 1570-1575. doi:  10.3969/j.issn.1001-5256.2019.07.029
    [21] JASMOHAN S B. Alcohol, liver disease and the gut microbiota[J]. Nature Reviews Gastroenterology & Hepatology,2019,16:235−246.
    [22] NAGA S B, PATRICK M G, JASMOHAN S B. Gut microbiome and liver disease[J]. Translational Research,2017,179:49−59. doi:  10.1016/j.trsl.2016.07.005
    [23] MING Lyu, WANG Yuefei. Balancing herbal medicine and functional food for prevention and treatment of cardiometabolic diseases through modulating gut microbiota[J]. Frontiers in Microbiology,2017,8:2146. doi:  10.3389/fmicb.2017.02146
    [24] LIN Tzulung, LU Chiachen, LAI Weifan, et al. Role of gut microbiota in identification of novel TCM-derived active metabolites[J]. Protein & Cell,2021,12:394−410.
    [25] LIU Meng, YUAN Jie, HU Wenjuan, et al. Pretreatment with broad-spectrum antibiotics alters the pharmacokinetics of major constituents of Shaoyao-Gancao decoction in rats after oral administration[J]. Pharmacologica Sinica,2019,40(2):288−296. doi:  10.1038/s41401-018-0011-0
    [26] LI Yun, LIU Tianyu, YAN Chen, et al. Diammonium glycyrrhizinate protects against non-alcoholic fatty liver disease in mice through modulation of gut microbiota and restoring intestinal barrier[J]. Molecular Pharmaceutics,2018,15(9):3860−3870. doi:  10.1021/acs.molpharmaceut.8b00347
    [27] ZHANG Feng, HE Fang, LI Li, et al. Bioavailability based on the gut microbiota: A new perspective[J]. Microbiology and Molecular Biology Reviews, 2020, 84(2):19.
  • 加载中
图(8)
计量
  • 文章访问数:  40
  • HTML全文浏览量:  7
  • PDF下载量:  12
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-11-15
  • 网络出版日期:  2022-05-14
  • 刊出日期:  2022-06-08

目录

    /

    返回文章
    返回

    重要通知

    《食品工业科技》青年编委专栏征稿 | 杂粮与主粮复配的营养学基础