Effects of<italic style="font-style: italic"> Yinqi Sanhuang Jiedu Decoction</italic> （茵芪三黄解毒汤） on Liver Hardness and Epithelial Mesenchymal Transition in Hepatic Fibrosis Model Mice

WANG Ning; LYU Wenliang; WU Qingjuan

doi:10.13288/j.11-2166/r.2023.17.012

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Effects of Yinqi Sanhuang Jiedu Decoction （茵芪三黄解毒汤） on Liver Hardness and Epithelial Mesenchymal Transition in Hepatic Fibrosis Model Mice

更新时间：2023-08-31

- Effects of Yinqi Sanhuang Jiedu Decoction （茵芪三黄解毒汤） on Liver Hardness and Epithelial Mesenchymal Transition in Hepatic Fibrosis Model Mice
- Journal of Traditional Chinese Medicine Vol. 64, Issue 17, Pages: 1792-1798(2023)
- 作者机构：
  
  中国中医科学院广安门医院，北京市西城区北线阁5号，100053
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.17.012
  CLC：
- Received：01 March 2023，
  
  Revised：2023-05-26，
  
  Published：02 September 2023
- 稿件说明：
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王宁,吕文良,武庆娟.茵芪三黄解毒汤对肝纤维化模型小鼠肝脏硬度及上皮间质转化的影响[J].中医杂志,2023,64(17):1792-1798.

WANG Ning,LYU Wenliang,WU Qingjuan.Effects of Yinqi Sanhuang Jiedu Decoction （茵芪三黄解毒汤） on Liver Hardness and Epithelial Mesenchymal Transition in Hepatic Fibrosis Model Mice[J].Journal of Traditional Chinese Medicine,2023,64(17):1792-1798.
王宁,吕文良,武庆娟.茵芪三黄解毒汤对肝纤维化模型小鼠肝脏硬度及上皮间质转化的影响[J].中医杂志,2023,64(17):1792-1798. DOI： 10.13288/j.11-2166/r.2023.17.012.

WANG Ning,LYU Wenliang,WU Qingjuan.Effects of Yinqi Sanhuang Jiedu Decoction （茵芪三黄解毒汤） on Liver Hardness and Epithelial Mesenchymal Transition in Hepatic Fibrosis Model Mice[J].Journal of Traditional Chinese Medicine,2023,64(17):1792-1798. DOI： 10.13288/j.11-2166/r.2023.17.012.

摘要

目的

探讨复方茵芪三黄解毒汤抗肝纤维化进展的可能作用机制。

方法

将38只C57BL/6J小鼠随机分为空白组、模型组、水飞蓟宾组和茵芪三黄解毒汤低、中、高剂量组，模型组8只，其余每组6只。除空白组外其余各组小鼠均腹腔注射10%四氯化碳（CCl

）建立肝纤维化模型，每周2次，持续8周。首次造模1周后开始药物干预，茵芪三黄解毒汤低、中、高剂量组分别给予茵芪三黄解毒汤混悬液8.325、16.65、33.3 g/（kg·d）灌胃，水飞蓟宾组给予水飞蓟宾混悬液55 mg/（kg·d）灌胃，空白组和模型组给予0.2 ml生理盐水灌胃，持续8周。使用小动物超声探测仪观察活体小鼠肝脏硬度记录超声灰度值，采用天狼猩红染色观察肝脏组织并计算胶原纤维沉积比例，检测各组小鼠肝功能［包括丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）］及血清中层粘连蛋白（LN）、透明质酸（HA）、Ⅲ型前胶原（PCⅢ）、Ⅳ型胶原（CⅣ）含量，检测小鼠肝组织中转化生长因子β1（TGF-β1）、波形蛋白（Vimentin）、E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）、α平滑肌肌动蛋白（α-SMA）蛋白表达。

结果

与空白组相比，模型组小鼠肝脏超声灰度值、胶原纤维沉积比例升高，血清ALT、AST、HA、LN、PCⅢ水平升高，肝组织中E-cadherin表达减少，N-cadherin、α-SMA、Vimentin、TGF-β1表达增加（

＜0.05）。与模型组比较，水飞蓟宾组与茵芪三黄解毒汤中、高剂量组肝脏超声灰度值及胶原纤维沉积比例下降，血清ALT、AST、LN、HA、PCⅢ水平降低；而与模型组相比，水飞蓟宾组和茵芪三黄解毒汤各剂量组小鼠肝组织中E-cadherin表达升高，N-cadherin、Vimentin、TGF-β1、α-SMA表达均下降（

＜0.05），其中茵芪三黄解毒汤中剂量组各项指标改善最为显著（

＜0.05）。

结论

茵芪三黄解毒汤能够显著减轻CCl

致小鼠肝纤维化的程度，可能与其调控肝脏硬度抑制小鼠上皮间质转化发生有关。

Abstract

Objective

To investigate the possible mechanism of compound

Yinqi Sanhuang Jiedu Decoction

（茵芪三黄解毒汤， YSJD） against the progression of hepatic fibrosis （HF）.

Methods

Thirty-eight C57BL/6J mice were randomly divided into blank group， model group， silybin group and low-， medium- and high-dose YSJD groups， with eight mice in the model group and six mice each in other groups. Except for the blank group， all mice were injected intraperitoneally with 10% carbon tetrachloride （CCl

） to establish a HF model， twice a week for 8 weeks. The drug intervention started one week after the first modeling； the low-， medium- and high-dose YSJD groups were given 8.325， 16.65 and 33.3 g/（kg·d） of YSJD suspension by gavage， respectively， while the silybin group was given 55 mg/（kg·d） of silybin suspension by gavage， and the blank group and the model group were given 0.2 ml normal saline by gavage， all for 8 weeks. The liver hardness of living mice was observed using a small animal ultrasound detector， and grey-scale ultrasound was recorded. The liver tissue was observed by Sirius scarlet staining， and the proportion of collagen fiber deposition was calculated. Liver function indicators including alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， and serum laminin （LN）， hyaluronic acid （HA）， pre-collagen type III （PCIII） and collagen type IV （CIV） were also detected. The protein expression of transforming growth factor β1 （TGF-β1）， Vimentin， E-cadherin， α smooth muscle actin （α-SMA） in liver tissue were detected.

Results

Compared to the blank group， the model group showed increased gray value， collagen deposition，serum ALT， AST， HA， LN and PCIII levels， decreased expression of E-cadherin， and increased expression of N-cadherin，α-SMA，Vimentin and TGF-β1 in liver tissues （

＜0.05）. Compared to the model group， the ultrasonic gray value and the proportion of collagen fiber deposition in liver of silybin group and YSJD medium- and high-dose groups decreased， and the serum ALT， AST， LN， HA and PCⅢ levels decreased. Compared to the model group， the expression of E-cadherin in liver tissues of silybin group and all three YSJD groups increased， while the expressions of N-cadherin， Vimentin， TGF-β1 and α-SMA decreased （

＜0.05）， and among them， most improvements were seen in the medium-dose YSJD group （

＜0.05）.

Conclusion

The effect of YSJD on significantly reducing the extent of HF in mice caused by CCl

may be related to its ability to regulate liver hardness and inhibit the occurrence of epithelial mesenchymal transition in mice.

关键词

Keywords

references

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Effects of Yinqi Sanhuang Jiedu Decoction （茵芪三黄解毒汤） on Liver Hardness and Epithelial Mesenchymal Transition in Hepatic Fibrosis Model Mice

DOI：10.13288/j.11-2166/r.2023.17.012

摘要

Abstract

关键词

Keywords

references