Effects of Modified <italic style="font-style: italic">Gegen Qinlian Decoction</italic> （葛根芩连汤） on Intestinal Mucosal Barrier and Epithelial Mesenchymal Transition in Ulcerative Colitis Model Mice

FANG Lihui; ZHANG Jiaqi; HU Lanshuo; WANG Xintong; LIU Shan; WANG Yuedan; HUANG Jinke; TANG Xudong

doi:10.13288/j.11-2166/r.2024.24.012

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Effects of Modified Gegen Qinlian Decoction （葛根芩连汤） on Intestinal Mucosal Barrier and Epithelial Mesenchymal Transition in Ulcerative Colitis Model Mice

更新时间：2026-02-03

- Effects of Modified Gegen Qinlian Decoction （葛根芩连汤） on Intestinal Mucosal Barrier and Epithelial Mesenchymal Transition in Ulcerative Colitis Model Mice
- Journal of Traditional Chinese Medicine Vol. 65, Issue 24, Pages: 2580-2588(2024)
- 作者机构：
  
  1.北京中医药大学研究生院，北京市朝阳区北三环东路11号，100029
  2.中国中医科学院西苑医院脾胃病研究所
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2024.24.012
  CLC：
- Received：25 July 2024，
  
  Revised：2024-09-23，
  
  Published：17 December 2024
- 稿件说明：
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方俐晖,张佳琪,胡蓝烁等.葛根芩连汤加味方对溃疡性结肠炎模型小鼠肠黏膜屏障及上皮间质转化的影响[J].中医杂志,2024,65(24):2580-2588.

FANG Lihui,ZHANG Jiaqi,HU Lanshuo,et al.Effects of Modified Gegen Qinlian Decoction （葛根芩连汤） on Intestinal Mucosal Barrier and Epithelial Mesenchymal Transition in Ulcerative Colitis Model Mice[J].Journal of Traditional Chinese Medicine,2024,65(24):2580-2588.
方俐晖,张佳琪,胡蓝烁等.葛根芩连汤加味方对溃疡性结肠炎模型小鼠肠黏膜屏障及上皮间质转化的影响[J].中医杂志,2024,65(24):2580-2588. DOI： 10.13288/j.11-2166/r.2024.24.012.

FANG Lihui,ZHANG Jiaqi,HU Lanshuo,et al.Effects of Modified Gegen Qinlian Decoction （葛根芩连汤） on Intestinal Mucosal Barrier and Epithelial Mesenchymal Transition in Ulcerative Colitis Model Mice[J].Journal of Traditional Chinese Medicine,2024,65(24):2580-2588. DOI： 10.13288/j.11-2166/r.2024.24.012.

摘要

目的

从上皮屏障损伤和上皮间质转化角度探讨葛根芩连汤加味方治疗溃疡性结肠炎的可能作用机制。

方法

将60只雄性C57BL/6J小鼠随机分为空白组、模型组、西药对照组和葛根芩连汤加味方低、中、高剂量组，每组10只。除空白组外其余各组小鼠采用3%葡聚糖硫酸钠自由饮用7天诱导结肠炎模型，造模第1天开始葛根芩连汤加味方低、中、高剂量组分别给予葛根芩连汤加味方6、12、24 g/（kg·d）灌胃，西药对照组给予5-氨基水杨酸100 mg/（kg·d）灌胃，空白组和模型组小鼠给予10 ml/kg蒸馏水灌胃，每日1次，共7天。每天记录小鼠体质量并进行疾病活动指数（DAI）评分。末次给药后24 h麻醉小鼠并取结肠观察结肠长度，应用HE染色观察结肠组织病理变化并进行病理组织学评分，Masson染色检测结肠胶原纤维面积占比，免疫荧光观察结肠黏膜上皮F-肌动蛋白（F-actin）分布表达，免疫组化检测紧密连接蛋白1（ZO-1）、闭合蛋白（Occludin）、E-钙黏蛋白（E-cadherin）和波形蛋白（Vimentin）表达。

结果

与空白组同时间比较，造模第7天模型组小鼠体质量百分比明显下降、DAI评分明显升高（

＜0.01）；与模型组同时间比较，西药对照组和葛根芩连汤加味方各剂量组小鼠的体质量下降，西药对照组和葛根芩连汤高剂量组DAI评分降低（

＜0.05或

＜0.01）；与葛根芩连汤低剂量组同时间比较，葛根芩连汤高剂量组和西药对照组小鼠体质量明显增加（

＜0.05）。与空白组比较，模型组小鼠结肠长度明显缩短，病理组织学评分、胶原面积占比明显升高，F-actin平均荧光强度降低，结肠组织ZO-1、Occludin、E-cadherin蛋白水平下降，Vimentin蛋白水平升高（

＜0.01）。与模型组比较，各给药组小鼠结肠长度明显增加，病理组织学评分、胶原面积占比降低，ZO-1、Occludin、E-cadherin蛋白水平升高，Vimentin水平降低；西药对照组和葛根芩连汤加味方中、高剂量组F-actin平均荧光强度增加（

＜0.05或

＜0.01）。与葛根芩连汤加味方低剂量组比较，葛根芩连汤加味方中剂量组及西药对照组胶原纤维面积占比降低；葛根芩连汤加味方中剂量组F-actin平均荧光强度升高；西药对照组ZO-1、E-cadherin蛋白水平升高，葛根芩连汤加味方高剂量组ZO-1蛋白水平升高（

＜0.05）。与葛根芩连汤加味方中剂量组比较，葛根芩连汤加味方高剂量组与西药对照组ZO-1蛋白水平升高（

＜0.05）。与葛根芩连汤加味方高剂量组比较，西药对照组E-cadherin、Vimentin蛋白水平均升高（

＜0.05）。

结论

葛根芩连汤加味方能够减轻溃疡性结肠炎模型小鼠结肠炎症及黏膜屏障损伤，抑制上皮间质转化进程，可能是其作用机制之一。

Abstract

Objective

To investigate the possible mechanism of modified

Gegen Qinlian Decoction

（葛根芩连汤） in treatment of ulcerative colitis （UC） from the view of intestinal mucosal epithelial barrier damage and epithelial mesenchymal transition.

Methods

Sixty male C57BL/6J mice were divided into blank group， model group， western medicine control group， and low-， medium-， and high-dose modified

Gegen Qinlian Decoction

groups， with 10 mice in each group. Except for the blank group， 3% dextran sodium sulfate （DSS） was used to induce colitis model by free drinking for 7 days， and on the first day of modelling， 6， 12， and 24 g/（kg·d） of modified

Gegen Qinlian Decoction

were given to the low-， medium-， and high-dose groups respectively， 5-aminosalicylic acid （5-ASA） 100 mg/（kg·d） given by gavage to western medicine control group， and 10 ml/kg distilled water were given to blank and model group by gavage， once a day for 7 days. Body mass of mice was recorded and disease activity index （DAI） scores were performed daily. The mice were anesthetized after 24h of the last administration and the colon was taken to observe the length of colon， HE staining was applied to observe the damage of colonic mucosa and score pathological states， Masson staining to detect the deposition of colonic collagen fibers， immunofluorescence to observe the distribution of F-actin in colonic mucosal epithelium， and immunohistochemistry to detect the expression of tight junction protein ZO-1， Occludin， E-cadherin and Vimentin.

Results

Compared with the blank group at the same time， the percentage of body mass of mice in the model group on day 7 of modelling significantly reduced and the DAI score was significantly increased （

＜0.01）； compared with the model group at the same time， the body mass of mice in the western medicine control group and all of modified

Gegen Qinlian Decoction

groups decreased， and the DAI scores of mice in the western medicine control group and the high-dose modified

Gegen Qinlian Decoction

group decreased （

＜0.05 or

＜0.01）； compared with the same time of mice in the low-dos

Gegen Qinlian Decoction

group， the body mass of mice in the high-dose

Gegen Qinlian Decoction

group and the western medicine control group significantly elevated （

＜0.05）. Compared with the blank group， the length of the colon of mice in the model group was significantly shortened， the pathological score and the percentage of collagen area were significantly increased， the average fluorescence intensity of F-actin was reduced， the p

rotein levels of ZO-1， Occludin and E-cadherin in the colon tissue decreased， and the protein level of Vimentin elevated （

＜0.01）. Compared with the model group， the length of colon significantly increased， patholo-gical score， collagen area percentage decreased， ZO-1， Occludin， E-cadherin protein levels increased and Vimentin levels decreased in all medicated groups； the average fluorescence intensity of F-actin increased in the western medicine control group and the middle- and high-dose

Gegen Qinlian Decoction

groups （

＜0.05 or

＜0.01）. Compared with the low-dose

Gegen Qinlian Decoction

group， the proportion of collagen fibre area in the middle-dose

Gegen Qinlian Decoction

group and the western medicine control group reduced； the mean fluorescence intensity of F-actin increased in the middle-dose

Gegen Qinlian Decoction

group； the protein levels of ZO-1 and E-cadherin increased in the western medicine control group， and the protein levels of ZO-1 increased in the high-dose

Gegen Qinlian Decoction

group （

＜0.05）. Compared with the medium-dose

Gegen Qinlian Decoction

group， the protein levels of ZO-1 elevated in the high-dose

Gegen Qinlian Decoction

group （

＜0.05）. Comapred with the high-dose

Gegen Qinlian Decoction

group， level of E-cadherin and Vimentin protein of the western medicine control group increased （

＜0.05）.

Conclusion

Modified

Gegen Qinlian Decoction

was able to reduce colonic inflammation and mucosal barrier damage and inhibit the process of epithelial mesenchymal transition in mice models of ulcerative colitis， which may be one of its action mechanisms .

关键词

Keywords

references

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Effects of Modified Gegen Qinlian Decoction （葛根芩连汤） on Intestinal Mucosal Barrier and Epithelial Mesenchymal Transition in Ulcerative Colitis Model Mice

DOI：10.13288/j.11-2166/r.2024.24.012

摘要

Abstract

关键词

Keywords

references