Mechanism of Tiaozhong huashi decoction in improving gastroesophageal reflux disease by restoring endoplasmic reticulum autophagy through p62 signaling pathway
- VernacularTitle:调中化湿汤通过p62信号通路恢复内质网自噬对胃食管反流病的改善作用机制
- Author:
Zezhong TENG
1
;
Nan CHEN
1
;
Yuqing WANG
1
;
Zuomei LUO
1
;
Guangwen CHEN
2
;
Liqun LI
2
;
Lijian LIU
2
;
Xueping ZHAO
3
;
Chengning YANG
2
Author Information
1. School of Graduate，Guangxi University of Chinese Medicine，Nanning 530023，China
2. Dept. of Spleen and Stomach Disease，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China
3. Preventive Treatment Center，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China
- Publication Type:Journal Article
- Keywords:
Tiaozhong huashi decoction;
Gastroesophageal reflux disease;
endoplasmic reticulum autophagy;
p62 signaling pathway;
interstitial cells of Cajal
- From:
China Pharmacy
2026;37(19):2516-2521
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the molecular mechanism of Tiaozhong huashi decoction in improving gastroesophageal reflux disease （GERD） by regulating endoplasmic reticulum autophagy in rat esophageal interstitial cells of Cajal （ICC） through p62 signaling pathway.METHODS After establishing a rat GERD model via the weak acid intragastric administration and irregular diet， the rats were randomly divided into model group， western medicine group [1.56 mg/（kg·d） of mosapride， 3.125 mg/（kg·d） of lansoprazole] and low-， medium- and high-dose Tiaozhong huashi decoction [4.713， 9.425， 18.85 g/（kg·d）] groups. A blank group was also set up， with 8 rats in each group. The rats in each group were intragastrically administered with corresponding liquid or normal saline twice a day for 14 days. During the intervention period， the general conditions of rats’ hair， spirit， diet and defecation were observed. After the last gavage， the pathological changes of esophageal tissue and the ultrastructure of ICC were observed. The relative expression and positive expression levels of p62， autophagy-related protein 8 （ATG8）， 200 kDa FAK family kinase-interacting protein （FIP200） and Unc-51 like autophagy activating kinase 1 （ULK1） in esophageal tissue were detected.RESULTS Compared with the blank group， rats in the model group exhibited listlessness； thickening of the esophageal basal layer， elongation of lamina propria papillae with inflammatory cell infiltration； markedly dilated endoplasmic reticulum appearing as round vacuolar cisternae with ribosome detachment； and a small number of accumulated autophagosomes. The relative expression and positive expression levels of p62， ATG8， FIP200， and ULK1 were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological injuries in the medium- and high-dose Tiaozhong huashi decoction groups had all improved to varying degrees； the damaged endoplasmic reticulum structure was repaired， and no autophagosome accumulation was observed. In particular， the relative expression levels and positive expression levels of p62， ATG8， FIP200， and ULK1 in esophageal tissue of rats in the medium-dose Tiaozhong huashi decoction group were significantly increased （ P ＜0.05）.CONCLUSIONS Tiaozhong huashi decoction ameliorated esophageal mucosal injury in GERD rats， and its mechanism was possibly associated with activation of the p62 signaling pathway and restoration of the endoplasmic reticulum structure， morphology， and autophagic capacity of ICC.
