Study on liver protection mechanism of Zhizi Bopi Decoction on cholestasis mice induced by cholic acid feeding

Yue LI; Guochao SONG; Xiaoqing XU; Bin ZOU; Jing ZHAO; Fengyi WENG; Si CHENG; Jingyi JIN; Dongming YAN; Bo TAN; Furong QIU

doi:10.16306/j.1008-861x.2022.S1.036

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Study on liver protection mechanism of Zhizi Bopi Decoction on cholestasis mice induced by cholic acid feeding

Experiment Research | 更新时间：2022-08-29

- Study on liver protection mechanism of Zhizi Bopi Decoction on cholestasis mice induced by cholic acid feeding
- Academic Journal of Shanghai University of Traditional Chinese Medicine Vol. 36, Issue S1, Pages: 154-160(2022)
- 作者机构：
  
  1.上海中医药大学附属曙光医院临床药代动力学实验室（上海　201203）
  2.上海中医药大学附属曙光医院检验科（上海　201203）
- 作者简介：
- 基金信息：
- DOI：10.16306/j.1008-861x.2022.S1.036
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李玥,宋国超,徐晓青等.栀子柏皮汤对胆酸饲料诱导胆汁淤积症小鼠肝保护机制研究[J].上海中医药大学学报,2022,36(S1):154-160.

LI Yue,SONG Guochao,XU Xiaoqing,et al.Study on liver protection mechanism of Zhizi Bopi Decoction on cholestasis mice induced by cholic acid feeding[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(S1):154-160.
李玥,宋国超,徐晓青等.栀子柏皮汤对胆酸饲料诱导胆汁淤积症小鼠肝保护机制研究[J].上海中医药大学学报,2022,36(S1):154-160. DOI： 10.16306/j.1008-861x.2022.S1.036.

LI Yue,SONG Guochao,XU Xiaoqing,et al.Study on liver protection mechanism of Zhizi Bopi Decoction on cholestasis mice induced by cholic acid feeding[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(S1):154-160. DOI： 10.16306/j.1008-861x.2022.S1.036.

摘要

目的,2,研究栀子柏皮汤对含1%胆酸（CA）饲料诱导胆汁淤积症小鼠的肝保护作用及其机制。,方法,2,C57BL/6雄性小鼠随机分为3组，即正常对照组、1% CA模型组、栀子柏皮汤组，每组5只。栀子柏皮汤组灌胃给予栀子柏皮汤（6 g/kg，每10 g 小鼠体质量0.1 ml），每日1次，连续10 d。正常对照组和1% CA模型组分别灌胃等体积0.9% NaCl溶液。所有组前3 d喂食正常饲料，于第4天灌胃后将1% CA模型组及栀子柏皮汤组换为含1% CA饲料饲养，直至实验结束，正常对照组仍继续用普通饲料饲养。干预结束后，检测小鼠血浆碱性磷酸酶（ALP）和丙氨酸转氨酶（ALT）活性；HE染色观察小鼠肝脏病理改变；LC-MS/MS检测小鼠肝脏胆汁酸含量；Western blot法测定小鼠肝脏Nod 样受体家族含pyrin 结构域蛋白3（NLRP3）炎性小体、衔接子（ASC）和消皮素D的N端剪切体（GSDMD-N）蛋白表达。,结果,2,与1% CA模型组比较，栀子柏皮汤组显著降低血浆ALT和ALP活性，缓解肝脏坏死及汇管区炎性细胞浸润，显著减少肝内总胆汁酸、牛磺胆酸（TCA）和牛磺脱氧胆酸（TDCA）的含量，并能下调NLRP3、ASC和GSDMD-N的蛋白表达，差异均有统计学意义（,P,<,0.05）。,结论,2,栀子柏皮汤对1% CA饲料诱导肝内胆汁淤积症小鼠具有肝保护作用，其机制可能与缓解肝内胆汁酸蓄积以及抑制NLRP3炎性小体活化、减少细胞焦亡有关。

Abstract

Objective： To study the,hepatoprotective effect of Zhizi Bopi Decoction on cholestasis mice induced by 1% cholic acid （CA） feeding， and explore the mechanism.,Methods,2,C57BL/6 male mice were randomly divided into 3 groups （,n,=5）： normal control group， 1% CA model group， Zhizi Bopi Decoction group. Zhizi Bopi decoction group was given Zhizi Bopi Decoction by gavage （6 g/kg， body weight 0.1 ml per 10 g）， once a day， for consecutive 10 days. Normal control group and 1% CA model group were given 0.9% NaCl solution by gavage. All groups were fed normal feed for the first 3 days， and 1% CA model group and Zhizi Bopi Decoction group were changed to 1% CA diet on the 4th day after intragastric administration until the end of the experiment. The normal control group continued to feed with ordinary feed. After intervention， plasma alkaline phosphatase （ALP） and alanine aminotransferase （ALT） activities were detected， and liver histopathology was performed by H,&,E staining. Hepatic bile acid contents were measured by LC-MS/MS， and expression of NOD‑like receptors family pyrin domain containing 3 （NLRP3） inflammasome， adaptor （ASC） and N-terminal clipping body of gasdermin D （GSDMD-N） in mouse liver was quantified by Western blot.,Results,2,Compared with 1% CA model group， the activities of ALT and ALP in plasma in Zhizi Bopi Decoction group were significantly decreased， liver necrosis and inflammatory cell infiltration were alleviated， the contents of hepatic total bile acid， taurocholic acid （TCA） and taurodeoxycholic acid （TDCA） in liver were significantly decreased， and the protein expressions of NLRP3， ASC and GSDMD-N were down-regulated. The differences were statistically significant（,P,<,0.05）.,Conclusion,2,Zhizi Bopi Decoction can protect the liver of mice against 1% CA feeding-induced cholestatic liver injury， which may be related to alleviating hepatic bile acid accumulation， inhibiting the activation of NLRP3 inflammasome and reducing pyroptosis.

关键词

栀子柏皮汤胆汁淤积症胆汁酸NLRP3炎性小体细胞焦亡

Keywords

Zhizi Bopi Decoctioncholestasisbile acidNLRP3 Inflammasomepyroptosis

references

曹旬旬，高月求，张文宏，等. 基于上海市住院慢性肝病患者胆汁淤积患病率的调查研究［J］.中华肝脏病杂志，2015，23（8）：569-573.

罗海静，成春锋. 栀子柏皮汤的现代研究进展［J］.中医药临床杂志，2018，30（9）：1754-1757.

高薇. 卢秉久经方治疗黄疸［J］. 实用中医内科杂志，2015，29（12）：14-15.

曹璐，李俊，黄成，等. 栀子柏皮汤对α-萘异硫氰酸酯诱导的肝内胆汁淤积大鼠的保护作用［J］.安徽医科大学学报，2013，48（3）：257-262.

肖旭，朱继孝，罗光明，等. 栀子柏皮汤对小鼠急性肝损伤的保护作用及对大鼠的利胆作用研究［J］. 时珍国医国药，2012，23（12）：2998-3000.

张超. 栀子柏皮汤对α-萘异硫氰酸酯致大鼠肝损伤的保护作用［J］. 时珍国医国药，2013，24（8）：1862-1864.

杨扬，吴小琴，李小枫，等. 栀子柏皮汤及含栀子配伍组对免疫性肝损伤小鼠的保护作用［J］. 中国药理学通报，2015，31（12）：1764-1769.

HOLTMANN T M， INZAUGARAT M E， KNORR J， et al. Bile aids activate NLRP3 inflammasome， promoting murine liver inflammation or fibrosis in a cell type-specific manner［J］. Cells， 2021， 10（10）： 2618.

MATHUR A， HAYWARD J A， MAN S M. Molecular mechanisms of inflammasome signaling［J］. J Leukoc Biol， 2018， 103（2）： 233-257.

WANG R， LAM P， LIU L， et al. Severe cholestasis induced by cholic acid feeding in knockout mice of sister of P-glycoprotein［J］. Hepatology， 2003， 38（6）：1489-1499.

MAILLETTE de BUY WENNIGER L， BEUERS U. Bile salts and cholestasis［J］. Dig Liver Dis， 2010， 42（6）： 409-418.

WANG L， WU G， WU F， et al. Geniposide attenuates ANIT-induced cholestasis through regulation of transporters and enzymes involved in bile acids homeostasis in rats［J］. J Ethnopharmacol， 2017（196）： 178-185.

WANG Y G， ZHOU J M， MA Z C， et al. Pregnane X receptor mediated-transcription regulation of CYP3A by glycyrrhizin： a possible mechanism for its hepatoprotective property against lithocholic acid-induced injury［J］. Chem Biol Interact， 2012， 200（1）： 11-20.

YANG L， MIZUOCHI T， SHIVAKUMAR P， et al. Regulation of epithelial injury and bile duct obstruction by NLRP3， IL-1R1 in experimental biliary atresia［J］. J Hepatol， 2018， 69（5）：1136-1144.

CAI S Y， GE M X， Mennone A， et al. Inflammasome is activated in the liver of cholestatic patients and aggravates hepatic injury in bile duct-ligated mouse［J］. Cell Mol Gastroenterol Hepatol， 2020， 9（4）： 679-688.

FRISSEN M， LIAO L， SCHNEIDER K M， et al. Bidirectional role of NLRP3 during acute and chronic cholestatic liver injury［J］. Hepatology， 2021， 73（5）： 1836-1854.

SZABO G， PETRASEK J. Inflammasome activation and function in liver disease［J］. Nat Rev Gastroenterol Hepatol， 2015， 12（7）： 387-400.

TIAN Z， LIU A， LUO M， et al. Geniposide inhibits Alpha-naphthylisothiocyanate-induced intrahepatic cholestasis： The downregulation of STAT3 and NF-κB signaling plays an important role［J］. Am J Chin Med， 2016， 44（4）： 721-736.

SU H， WANG Q， LI Y， et al. Effect of different ratios of Yinchen and Gancao Decoction on ANIT-treated cholestatic liver injury in mice and its potential underlying mechanism［J］. Front Pharmacol， 2021（12）： 611610.

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