Effects and mechanism of Hugan buzure formula on intrahepatic cholestatic liver injury in rats

Ayiziba·Tuerhong; YANG Jianhua; WANG Xiaomei; WANG Xinling; HU Junping

doi:10.6039/j.issn.1001-0408.2023.16.05

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Effects and mechanism of Hugan buzure formula on intrahepatic cholestatic liver injury in rats

更新时间：2023-08-24

- Effects and mechanism of Hugan buzure formula on intrahepatic cholestatic liver injury in rats
- ZHONGGUO YAOFANG Vol. 34, Issue 16, Pages: 1943-1948(2023)
- 作者机构：
  
  1.新疆医科大学药学院，乌鲁木齐　830011
  2.新疆医科大学第一附属医院药学部，乌鲁木齐　830011
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.16.05
  CLC： R965
- Published：30 August 2023，
  
  Received：24 March 2023，
  
  Revised：19 July 2023，
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阿依孜巴·图尔洪 ,杨建华,王晓梅等.护肝布祖热方对大鼠肝内胆汁淤积性肝损伤的影响及机制 ^Δ[J].中国药房,2023,34(16):1943-1948.

Ayiziba·Tuerhong ,YANG Jianhua,WANG Xiaomei,et al.Effects and mechanism of Hugan buzure formula on intrahepatic cholestatic liver injury in rats[J].ZHONGGUO YAOFANG,2023,34(16):1943-1948.
阿依孜巴·图尔洪 ,杨建华,王晓梅等.护肝布祖热方对大鼠肝内胆汁淤积性肝损伤的影响及机制 ^Δ[J].中国药房,2023,34(16):1943-1948. DOI： 10.6039/j.issn.1001-0408.2023.16.05.

Ayiziba·Tuerhong ,YANG Jianhua,WANG Xiaomei,et al.Effects and mechanism of Hugan buzure formula on intrahepatic cholestatic liver injury in rats[J].ZHONGGUO YAOFANG,2023,34(16):1943-1948. DOI： 10.6039/j.issn.1001-0408.2023.16.05.

摘要

目的

研究护肝布祖热方（HBF）对大鼠肝内胆汁淤积性肝损伤的影响及潜在机制。

方法

将大鼠随机分为对照组（control组）、模型组（model组）、熊去氧胆酸（UDCA）组（阳性对照，60 mg/kg）和HBF低、中、高剂量组（HBF-L、HBF-M、HBF-H组，0.4、0.8、1.6 g/kg），每组6只。各药物组大鼠每天灌胃相应药液1次，连续7 d；control组和model组大鼠灌胃等体积水。实验第5天，除control组外，其余各组大鼠均单次灌胃

-异硫氰酸萘酯橄榄油溶液（100 mg/kg）建模。造模48 h后，检测大鼠血清中肝功能指标（天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、总胆汁酸、总胆红素、直接胆红素）含量和氧化应激指标[丙二醛（MDA）、谷胱甘肽（GSH）、超氧化物歧化酶]水平，观察肝组织病理形态变化，检测肝组织中炎症相关因子[肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）]

和法尼酯X受体（FXR）信号通路相关因子[FXR、小异源二聚体伴侣受体（SHP）、多药耐药蛋白2（MRP2）、胆盐输出泵转运蛋白（BSEP）、钠离子依赖性牛磺胆酸共转运蛋白（NTCP）、有机阴离子转运多肽2（OATP2）和胆固醇7α羟化酶（CYP7A1）]mRNA，以及FXR信号通路相关蛋白（FXR、MRP2、BSEP、NTCP）和核因子κB p65（NF-κB p65）蛋白的表达情况。

结果

与model组比较，HBF-H组大鼠血清中上述肝功能指标含量和MDA水平，肝组织中上述炎症相关因子mRNA、CYP7A1 mRNA的表达水平以及NF-κB p65蛋白的相对表达量均显著降低，血清中GSH水平和肝组织中FXR、SHP、MRP2、BSEP、NTCP、OATP2 mRNA的表达水平以及FXR、MRP2、BSEP、NTCP蛋白的相对表达量均显著升高（

＜0.05或

＜0.01），肝组织病理改变明显好转；HBF-L组、HBF-M组、UDCA组大鼠均只有部分指标显著逆转（

＜0.05或

＜0.01）。

结论

HBF可预防大鼠肝内胆汁淤积性肝损伤，此作用可能与激活FXR信号通路、减轻炎症和氧化应激有关。

Abstract

OBJECTIVE

To study the effects of Hugan buzure formula （HBF） on intrahepatic cholestatic liver injury in rats and its potential mechanism.

METHODS

Rats were randomly divided into control group， model group， ursodeoxycholic acid （UDCA） group （positive control， 60 mg/kg ） and HBF low-dose， middle-dose and high-dose groups （HBF-L， HBF-M， HBF-H groups， 0.4， 0.8， 1.6 g/kg ）， with 6 rats in each group. The rats in each drug group were given the corresponding drug solution intragastrically， once a day， for 7 consecutive days. The rats in the control group and the model group were given equal volumes of water intragastrically. On the 5th day， except for the control group， the rats in other groups were single intragastrically administered with alpha-naphthyl isothiocyanate olive oil solution （100 mg/kg） to establish the model. After 48 h of modeling， the contents of liver function indexes （aspartate aminotransferase， alanine aminotransferase， alkaline phosphatase， total bile acid， total bilirubin， direct bilirubin） and oxidative stress indexes [malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase] in serum of rats were detected； the pathological changes of liver tissue were observed. The mRNA expressions of inflammation-related factors [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）]

and farnesoid X receptor （FXR） signaling pathway-related factors [FXR， small heterodimer partner （SHP）， multidrug resistance protein 2 （MRP2）， bile salt export pump （BSEP）， Na

-taurocholate cotransporting polypeptide （NTCP）， organic anion-transporting polypeptide 2 （OATP2） and cholesterol 7α-hydroxylase （CYP7A1）]， the expressions of FXR signaling pathway-related proteins （FXR， MRP2， BSEP， NTCP） and nuclear factor-κB p65 （NF-κB p65） in liver tissue were detected.

RESULTS

Compared with the model group， the contents of liver function indexes and the level of MDA in serum， the mRNA expressions of the above inflammation-related factors and CYP7A1， and the relative expression of NF-κB p65 in liver tissue were significantly decreased； the levels of GSH in serum， the mRNA expressions of FXR， SHP， MRP2， BSEP， NTCP and OATP2， and the relative expressions of FXR， MRP2， BSEP and NTCP in liver tissue were significantly increased （

＜0.05 or

＜0.01）； the pathological changes of liver tissue were significantly improved. Only some indexes in HBF-L group， HBF-M group and UDCA group were significantly reversed （

＜0.05 or

＜0.01）.

CONCLUSIONS

HBF can prevent intrahepatic cholestatic liver injury in rats， and the effects may be related to the activation of FXR signaling pathway and the reduction of inflammation and oxidative stress.

关键词

护肝布祖热方肝内胆汁淤积性肝损伤法尼酯X受体信号通路炎症反应氧化应激

Keywords

intrahepatic cholestatic liver injuryfarnesoid X receptor signaling pathwayinflammatory reactionoxidative stress

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