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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 10
Oct.  2023
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Article Contents

Therapeutic effect of retention enema with compound rhubarb decoction on a rat model of minimal hepatic encephalopathy based on bile acid metabolomics

DOI: 10.3969/j.issn.1001-5256.2023.10.012
Research funding:

National Natural Science Foundation of China (81804019‍);

Guangxi Natural Science Foundation (2020GXNSFBA297033);

Guangxi Natural Science Foundation (2022GXNSFAA035460);

Guangxi Natural Science Foundation (2022GXNSFBA035485);

Guangxi Natural Science Foundation (2018GXNSFBA050041);

Innovation Project of Guangxi Graduate Education (YCBXJ2021013);

Innovation Project of Guangxi Graduate Education (YCXJ2021056);

Research Project of Traditional Chinese Medicine Zhuang Yao Treatment of Dominant Diseases (GZBZ22-3)

More Information
  • Corresponding author: WANG Meng, 46636308@qq.com (ORCID: 0000-0003-3935-3746)
  • Received Date: 2023-02-19
  • Published Date: 2023-10-30
  •   Objective  To investigate the therapeutic effect of rhubarb decoction (RD) retention enema on a rat model of minimal hepatic encephalopathy (MHE) and its mechanism of action based on bile acid (BA) metabolomics.  Methods  A total of 55 male Sprague-Dawley rats were randomly divided into blank group (NC group with 10 rats), hepatic encephalopathy group (HE group with 15 rats), MHE group with 15 rats, and MHE+rhubarb decoction treatment group (MHEY group with 15 rats). Intraperitoneal injection of carbon tetrachloride (CCl4) and thioacetamide (TAA) was performed to establish a rat model of MHE or HE, and the rats were sacrificed after 2 weeks of administration. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBil), and total bile acid (TBA) and the concentration of blood ammonia were measured; the colonic contents were collected to measure pH value; liver and brain tissue samples were collected, and HE staining was used to observe the histopathological changes of the liver; the bile was collected, and liquid chromatography-mass spectrometry was used to perform BA-targeted metabolomics analysis. Continuous data were expressed as mean±standard deviation; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups.  Results  Compared with the NC group, the HE group and the MHE group had a significant increase in searching platform latency (after modelling and after administration) and a significant reduction in the number of platform crossings (all P<0.05); compared with the MHE group, the MHEY group had a significant reduction in searching platform latency (after administration) and a significant increase in the number of platform crossings, and the HE group had a significant increase in searching platform latency and a significant reduction in the number of platform crossings (all P<0.05). Compared with the NC group, the HE group and the MHE group had significant increases in AST, ALT, ALP, TBil, TBA, blood ammonia, and colon pH value (all P<0.05); compared with the MHE group, the MHEY group had significant reductions in AST, ALT, ALP, TBil, TBA, blood ammonia, and colon pH value (all P<0.05), and the HE group had significant increases in AST, ALT, ALP, TBil, TBA, blood ammonia, and colon pH value (all P<0.05). The MHE group had significantly lower TBA, primary BA, and secondary BA than the NC group (all P<0.05); compared with the MHE group, the HE group had significantly lower TBA and primary BA (all P<0.05), and the MHEY group had significantly higher TBA and primary BA (all P<0.05). Compared with the NC group, the MHE group had significant reductions in GCDCA, GUDCA, GHDCA, TCDCA, TUDCA, GLCA, and TLCA (all P<0.05) and significant increases in γ-MCA, THCA, 7-KDCA, AlloLCA, and α-MCA (all P<0.05), and compared with the MHE group, the MHEY group had significant increases in THDCA, TMCA, TCDCA, TUDCA, and TLCA (all P<0.05).  Conclusion  RD retention enema can improve liver injury and cognitive function in a rat model of MHE induced by CCl4 and TAA by regulating the enterohepatic circulation of BA, possibly by increasing the synthesis of taurine-binding BA.

     

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  • [1]
    BAJAJ JS, WADE JB, SANYAL AJ. Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy[J]. Hepatology, 2009, 50( 6): 2014- 2021. DOI: 10.1002/hep.23216.
    [2]
    ELSAID MI, RUSTGI VK. Epidemiology of hepatic encephalopathy[J]. Clin Liver Dis, 2020, 24( 2): 157- 174. DOI: 10.1016/j.cld.2020.01.001.
    [3]
    DHAREL N, BAJAJ JS. Definition and nomenclature of hepatic encephalopathy[J]. J Clin Exp Hepatol, 2015, 5( Suppl 1): S37-S41. DOI: 10.1016/j.jceh.2014.10.001.
    [4]
    BAJAJ JS, DUARTE-ROJO A, XIE JJ, et al. Minimal hepatic encephalopathy and mild cognitive impairment worsen quality of life in elderly patients with cirrhosis[J]. Clin Gastroenterol Hepatol, 2020, 18( 13): 3008- 3016. e 2. DOI: 10.1016/j.cgh.2020.03.033.
    [5]
    PATEL D, MCPHAIL MJ, COBBOLD JF, et al. Hepatic encephalopathy[J]. Br J Hosp Med(Lond), 2012, 73( 2): 79- 85. DOI: 10.12968/hmed.2012.73.2.79.
    [6]
    HOLECEK M. Evidence of a vicious cycle in glutamine synthesis and breakdown in pathogenesis of hepatic encephalopathy-therapeutic perspectives[J]. Metab Brain Dis, 2014, 29( 1): 9- 17. DOI: 10.1007/s11011-013-9428-9.
    [7]
    JOHANSSON M, AGUSTI A, LLANSOLA M, et al. GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy[J]. Am J Physiol Gastrointest Liver Physiol, 2015, 309( 5): G400-G409. DOI: 10.1152/ajpgi.00073.2015.
    [8]
    LLANSOLA M, MONTOLIU C, AGUSTI A, et al. Interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in minimal hepatic encephalopathy[J]. Neurochem Int, 2015, 88: 15- 19. DOI: 10.1016/j.neuint.2014.10.011.
    [9]
    MCMILLIN M, GRANT S, FRAMPTON G, et al. FXR-Mediated cortical cholesterol accumulation contributes to the pathogenesis of type A hepatic encephalopathy[J]. Cell Mol Gastroenterol Hepatol, 2018, 6( 1): 47- 63. DOI: 10.1016/j.jcmgh.2018.02.008.
    [10]
    XUTIAN S, CAO D, WOZNIAK J, et al. Comprehension of the unique characteristics of traditional Chinese medicine[J]. Am J Chin Med, 2012, 40( 2): 231- 244. DOI: 10.1142/S0192415X12500188.
    [11]
    ZHANG X, YANG Y, ZHANG F, et al. Traditional Chinese medicines differentially modulate the gut microbiota based on their nature(Yao-Xing)[J]. Phytomedicine, 2021, 85: 153496. DOI: 10.1016/j.phymed.2021.153496.
    [12]
    WANG N, WANG MG, MAO DW, et al. Clinical efficacy observation of rhubarb decoction in the treatment of type A hepatic encephalopathy[J]. Lishizhen Med Mater Med Res, 2015, 26( 5): 1169- 1171. DOI: 10.3969/j.issn.1008-0805.2015.05.053.

    王娜, 王明刚, 毛德文, 等. 大黄煎剂治疗A型肝性脑病的临床疗效观察[J]. 时珍国医国药, 2015, 26( 5): 1169- 1171. DOI: 10.3969/j.issn.1008-0805.2015.05.053.
    [13]
    ZHANG GG. Effects of Rhubarb Decoction retention enema on the levels of endotoxin and blood ammonia in patients with mild hepatic encephalopathy[J]. J Pract Tradit Chin Med, 2018, 34( 5): 523- 524. DOI: 10.3969/j.issn.1004-2814.2018.05.013.

    张贵格. 大黄煎剂保留灌肠治疗轻微型肝性脑病对内毒素及血氨水平的影响[J]. 实用中医药杂志, 2018, 34( 5): 523- 524. DOI: 10.3969/j.issn.1004-2814.2018.05.013.
    [14]
    HUANG GC, WANG M, YANG XH, et al. Analysis of specific metabolite profiling of minimal hepatic encephalopathy based on metabolomics analytical plat-forms of GC-TOFMS and UPLC-QTOFMS[J]. J Clin Hepatol, 2016, 32( 1): 139- 142. DOI: 10.3969/j.issn.1001-5256.2016.01.027.

    黄国初, 王萌, 杨小徽, 等. 基于GC-TOFMS和UPLC-QTOFMS代谢组学分析平台对轻微型肝性脑病特异性代谢物谱的分析[J]. 临床肝胆病杂志, 2016, 32( 1): 139- 142. DOI: 10.3969/j.issn.1001-5256.2016.01.027.
    [15]
    HUANG GC, WANG M, YANG XH, et al. Effect of Dahuang decoction retention enema on serum metabolite profiling in patients with minimal hepatic encephalopathy[J]. JCM, 2016, 57( 3): 220- 223. DOI: 10.13288/j.11-2166/r.2016.03.011.

    黄国初, 王萌, 杨小徽, 等. 大黄煎剂保留灌肠对轻微型肝性脑病患者血清代谢物谱的影响[J]. 中医杂志, 2016, 57( 3): 220- 223. DOI: 10.13288/j.11-2166/r.2016.03.011.
    [16]
    LIU J, ZHU JZ, SUI YL, et al. Establishment of a rat model of hepatic encephalopathy[J]. Chin J Comp Med, 2012, 22( 2): 33- 37. DOI: 10.3969/j.issn.1671.7856.2012.02.008.

    刘冀, 朱建忠, 隋月林, 等. 四氯化碳诱导大鼠肝性脑病模型的制备[J]. 中国比较医学杂志, 2012, 22( 2): 33- 37. DOI: 10.3969/j.issn.1671.7856.2012.02.008.
    [17]
    ZHANG MH, JIA L, DU H, et al. Dose-effect of thioacetamide on animal model of hepatic encephalopathy in rats[J]. Acad J Guangzhou Med Coll, 2004, 32( 3): 72- 74. DOI: 10.3969/j.issn.1008-1836.2004.03.022.

    张美华, 贾林, 杜洪, 等. 硫代乙酰胺致大鼠肝性脑病模型的量-效关系[J]. 广州医学院学报, 2004, 32( 3): 72- 74. DOI: 10.3969/j.issn.1008-1836.2004.03.022.
    [18]
    JIA L. ZHANG MH, SU CA, et al. Establishment of a rat model of mild and micro hepatic encephalopathy induced by thioacetamide[J]. World Chin J Dig, 2004, 12( 5): 1207- 1208. DOI: 10.3969/j.issn.1009-3079.2004.05.046.

    贾林, 张美华, 苏常青, 等. 硫代乙酰胺致大鼠轻微型肝性脑病模型的建立[J]. 世界华人消化杂志, 2004, 12( 5): 1207- 1208. DOI: 10.3969/j.issn.1009-3079.2004.05.046.
    [19]
    ZIMMERMANN C, FERENCI P, PIFL C, et al. Hepatic encephalopathy in thioacetamide-induced acute liver failure in rats: characterization of an improved model and study of amino acid-ergic neurotransmission[J]. Hepatology, 1989, 9( 4): 594- 601. DOI: 10.1002/hep.1840090414.
    [20]
    MARGOLIS KG, CRYAN JF, MAYER EA. The microbiota-gut-brain axis: from motility to mood[J]. Gastroenterology, 2021, 160( 5): 1486- 1501. DOI: 10.1053/j.gastro.2020.10.066.
    [21]
    TIAN M, ZHENG D, LIU CL. Research progress on the involvement of gut microbiota in the pathogenesis of depression[J]. Chin J Med Offic, 2022, 50( 6): 658- 660. DOI: 10.16680/j.1671-3826.2022.06.34.

    田明, 郑丹, 刘春龙. 肠道微生物参与抑郁症发病机制研究进展[J]. 临床军医杂志, 2022, 50( 6): 658- 660. DOI: 10.16680/j.1671-3826.2022.06.34.
    [22]
    FASULLO M, RAU P, LIU DQ, et al. Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients[J]. World J Hepatol, 2019, 11( 6): 522- 530. DOI: 10.4254/wjh.v11.i6.522.
    [23]
    ZHENG X, CHEN T, ZHAO A, et al. The brain metabolome of male rats across the lifespan[J]. Sci Rep, 2016, 6: 24125. DOI: 10.1038/srep24125.
    [24]
    XIE G, ZHONG W, LI H, et al. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption[J]. FASEB J, 2013, 27( 9): 3583- 3593. DOI: 10.1096/fj.13-231860.
    [25]
    MANO N, SATO Y, NAGATA M, et al. Bioconversion of 3beta-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems[J]. J Lipid Res, 2004, 45( 9): 1741- 1748. DOI: 10.1194/jlr.M400157-JLR200.
    [26]
    KIRIYAMA Y, NOCHI H. The biosynthesis, signaling, and neurological functions of bile acids[J]. Biomolecules, 2019, 9( 6): 232. DOI: 10.3390/biom9060232.
    [27]
    WU X, LV YG, DU YF, et al. Neuroprotective effects of INT-777 against Aβ1-42-induced cognitive impairment, neuroinflammation, apoptosis, and synaptic dysfunction in mice[J]. Brain Behav Immun, 2018, 73: 533- 545. DOI: 10.1016/j.bbi.2018.06.018.
    [28]
    DEMORROW S. Bile acids in hepatic encephalopathy[J]. J Clin Exp Hepatol, 2019, 9( 1): 117- 124. DOI: 10.1016/j.jceh.2018.04.011.
    [29]
    JIA W, XIE G, JIA W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J]. Nat Rev Gastroenterol Hepatol, 2018, 15( 2): 111- 128. DOI: 10.1038/nrgastro.2017.119.
    [30]
    TAYYAR AT, TAYYAR A, KOZALI S, et al. Evaluation of FGF-19 and β-klotho as biomarkers in patients with intrahepatic cholestasis of pregnancy[J]. Arch Med Sci, 2019, 15( 1): 113- 119. DOI: 10.5114/aoms.2017.72424.
    [31]
    AHLUWALIA V, BETRAPALLY NS, HYLEMON PB, et al. Impaired gut-liver-brain axis in patients with cirrhosis[J]. Sci Rep, 2016, 6: 26800. DOI: 10.1038/srep26800.
    [32]
    MCMILLIN M, FRAMPTON G, QUINN M, et al. Bile acid signaling is involved in the neurological decline in a murine model of acute liver failure[J]. Am J Pathol, 2016, 186( 2): 312- 323. DOI: 10.1016/j.ajpath.2015.10.005.
    [33]
    QUINN M, MCMILLIN M, GALINDO C, et al. Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms[J]. Dig Liver Dis, 2014, 46( 6): 527- 534. DOI: 10.1016/j.dld.2014.01.159.
    [34]
    MCMILLIN M, FRAMPTON G, QUINN M, et al. Bile acid signaling is involved in the neurological decline in a murine model of acute liver failure[J]. Am J Pathol, 2016, 186( 2): 312- 323. DOI: 10.1016/j.ajpath.2015.10.005.
    [35]
    MAHMOUDIANDEHKORDI S, ARNOLD M, NHO K, et al. Altered bile acid profile associates with cognitive impairment in Alzheimer’s disease-An emerging role for gut microbiome[J]. Alzheimers Dement, 2019, 15( 1): 76- 92. DOI: 10.1016/j.jalz.2018.07.217.
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