Abstract：Objective: To explore the improvement effect of Danggui Zhuyu decoction on gastroesophageal reflux disease (GERD) rats and to preliminarily investigate its possible mechanism based on the NF-κB/MAPK signaling pathway. Methods: The GERD rat model was established by esophageal stent implantation. The rats were randomly divided into a sham operation group, a model group, a western medicine group (Moxapride citrate dispersed tablet 1.56 mg/kg and Lansoprazole enteric-coated tablet 3.125 mg/kg, gavage), Danggui Zhuyu decoction group (3.0 mg/kg Danggui Zhuyu decoction), with 15 rats in each group (3.0 mg/kg Angelica Chuyu Decoction + 10 mg/kg intraperitoneal injection of NF-κB pathway activator BA). The general state of each group was recorded during treatment. Hematoxylin-eosin (H&E) staining was used to analyze pathological histology of esophageal tissues. ELISA kit was applied to detect levels of TNF-α, IL-6, and IL-1β in esophageal tissues.RT-qPCR was performed to detect mRNA levels of macrophage polarization markers CD86, iNOS, and CD206 in esophageal tissues. Western Blot was used to detect expressions of E-cadherin, Claudin-4, and proteins related to NF-κB/MAPK signaling pathway. Results: Compared with the sham operation group, the model group had dull hair, reduced food intake, water intake, and body weight, dry feces with decreased volume, food residue reflux to the corners of the mouth, squamous epithelial hyperplasia in esophageal mucosa, lamina propria papilla extension, massive diffuse inflammatory cell infiltration, significantly increased TNF-α, IL-6, IL-1β, CD86 and iNOS mRNA, p-p65, p-JNK, p-ERK (P<0.05), and significantly decreased CD206 mRNA, E-cadherin, and Claudin-1 (P<0.05). Compared with the model group, the western medicine group, Danggui Zhuyu decoction group, and NF-κB activator group showed improved hair gloss, food intake, water intake, and feces condition, reduced dry or moist feces, decreased food residue reflux, increased body weight, attenuated esophageal mucosal squamous epithelial hyperplasia, lamina propria elongation, and inflammatory cell infiltration, significantly decreased TNF-α, IL-6, IL-1β, CD86 and iNOS mRNA, p-p65, p-JNK, p-ERK (P<0.05), and significantly increased CD206 mRNA, E-cadherin, and Claudin-1 (P<0.05). Compared with the western medicine group, the Danggui Zhuyu decoction group and NF-κB activator group had slight mucosal squamous epithelial hyperplasia and inflammatory cell infiltration, reduced lamina propria extension, significantly decreased TNF-α, IL-6, IL-1β, CD86 and iNOS mRNA, p-p65, p-JNK, p-ERK (P<0.05), and significantly increased CD206 mRNA, E-cadherin, and Claudin-1 (P<0.05). Compared with the Danggui Zhuyu decoction group, the NF-κB activator group had more inflammatory cell infiltration, squamous epithelial hyperplasia, and lamina propria extension, significantly increased TNF-α, IL-6, IL-1β, CD86 and iNOS mRNA, p-p65, p-JNK, p-ERK (P<0.05), and significantly decreased CD206 mRNA, E-cadherin, and Claudin-1 (P<0.05). Conclusion: Danggui Zhiru Decoction can improve GERD, regulate macrophage polarization to inhibit inflammatory responses, and enhance the function of the epithelial mucosal barrier. Its mechanism may be related to the inhibition of the NF-κB/MAPK signaling pathway.
2025, Vol. 31 
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