Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats

Xiao-lan YIN; Linda ZHONG; Cheng-yuan LIN; Xiao-shuang SHI; Jiao ZHANG; Zheng-yi CHEN; Hui CHE; Xiang-xue MA; Ya-xin TIAN; Yuan-zhi DUAN; Lin LU; Hai-jie JI; Ying-pan ZHAO; Xu-dong TANG; Feng-yun WANG

doi:10.1007/s11655-019-3027-5

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Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats

Original Article | Updated：2021-09-01

- Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats
- Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats
- Chinese Journal of Integrative Medicine 2021年27卷第8期页码：604-612
- Affiliations：
  
  1.Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing(100091), China
  2.School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, China
  3.Department of Gastroenterology, Changping Hospital of Traditional Chinese Medicine, Beijing(102200), China
  4.Department of Traditional Chinese Medicine, Dongfeng General Hospital, Shiyan (442000), Hubei Province, China
  5.Center of Clinical Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China
- Author bio：
  
  Dr. WANG Feng-yun, E-mail: wfy811@163.com
- Funds：
  
  Natural Science Foundation of China(81503560);"Ten Diseases and Ten Drugs" Program and the Cultivation Research of Biological Medicine and Life Science Innovation of Beijing Municipal Science and Technology Commission(Z141100002214012;Z161100000116046)
- DOI：10.1007/s11655-019-3027-5
  中图分类号：
- 纸质出版日期：2021-08-01，
  
  网络出版日期：2020-04-04，
  
  录用日期：2017-11-09
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Xiao-lan YIN, Linda ZHONG, Cheng-yuan LIN, 等. Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats[J]. Chinese Journal of Integrative Medicine, 2021,27(8):604-612.

Xiao-lan YIN, Linda ZHONG, Cheng-yuan LIN, et al. Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats[J]. Chinese Journal of Integrative Medicine, 2021,27(8):604-612.
Xiao-lan YIN, Linda ZHONG, Cheng-yuan LIN, 等. Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats[J]. Chinese Journal of Integrative Medicine, 2021,27(8):604-612. DOI： 10.1007/s11655-019-3027-5.

Xiao-lan YIN, Linda ZHONG, Cheng-yuan LIN, et al. Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats[J]. Chinese Journal of Integrative Medicine, 2021,27(8):604-612. DOI： 10.1007/s11655-019-3027-5.

摘要

Abstract

Objective:

To investigate the mechanism of Tojapride

a Chinese herbal formula extract

on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE).

Methods:

Ten out of 85 SD rats were randomly selected as the sham group (

=10)

and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model

low-

medium-

and highdose of Tojapride as well as omeprazole groups (

=10). Three doses of Tojapride [5.73

11.46

22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)]

were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered with 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume

pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining

and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κBp65)

κB kinase beta (IKKβ)

occludin

and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot

respectively.

Results:

The gastric pH value in the model group was significantly lower than the sham group (

0.05). Compared with the model group

gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (

0.05). A large area of ulceration was found on the esophageal mucosa from the model rats

while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group

the IKKβ levels were significantly higher in the model group (

0.05). However

the IKKβ levels were down-regulated after treatment by all doses of Tojapride (

0.01 or

0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (

0.01 or

0.05)

while both indices were significantly up-regulated in the Tojapride-treated groups (

0.01 or

0.05).

Conclusions:

Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKβ expression and elevating ZO-1 and occludin expression

thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

关键词

Keywords

reflux-esophagitistojaprideesophageal epithelial barrieranti-inflammatory

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