The comorbidity rate of gastroesophageal reflux disease （GERD） and sleep disorders is high， and the two form a vicious circle through the “brain-gut axis”， which seriously impacts the patients’ quality of life. Traditional Chinese medicine （TCM）， guided by the core principles of “holistic concept” and “syndrome differentiation and treatment”， features multi-targeted therapeutic effects with minimal side effects， offering diverse intervention options for clinical practice. From the perspective of the “brain-gut axis”， this article reviews the relationship between the comorbidity of GERD and sleep disorders and systematically examines relevant research findings on how TCM regulates the “brain-gut axis” to intervene in this comorbid condition. The study reveals that the “brain-gut axis” may participate in the pathological progress of GERD accompanied by sleep disorders through pathways such as abnormalities in the secretion of brain-gut peptides （including gastrointestinal secretin）， as well as intestinal dysbiosis. By closely focusing on core pathogenic mechanisms such as “disharmony between the liver and stomach” and “insomnia due to stomach disharmony”， various approaches can be employed， including TCM formulas （e.g.， modified Sini powder combined with Zuojin pills）， external TCM therapies （e.g.， back-shu point digital acupressure）， and integrated traditional Chinese and Western medicine treatments （e.g.， modified Chaihu guizhi ganjiang decoction combined with proton pump inhibitors）. These methods can regulate the levels of neurotransmitters， gastrointestinal hormones， inflammatory factors， and the composition of intestinal microbiota associated with the “brain-gut axis”， thereby achieving simultaneous improvement in both GERD and sleep disorders.

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.