Exploration of Huayu Xiaopi Decoction on Improving Gastric Mucosal Injury in Rats with Precancerous Lesions of Gastric Cancer Based on IL-6/JAK2/STAT3 Pathway
Objective To explore the effect and mechanism of Huayu Xiaopi Decoction on gastric mucosal injury in rats with precancerous lesions of gastric cancer(PLGC) based on the interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transduction and transcription activating factor 3 (STAT3) pathway. Methods Totally 10 SD rats were randomly selected as a blank group and the remaining 50 rats were used as a model group,which were replicated using a multi-factor comprehensive modeling method. After the PLGC model was successfully constructed,rats were randomly divided into model group,folic acid group(0.002 g·kg-1),low-,medium-and high-dose of Huayu Xiaopi Decoction(6.2,12.4,24.8 g·kg-1) groups,and then the corresponding drug was orally administered once a day for three months. The general condition,the body weight and 3-hour food intake of rats were observed. The pathological changes of gastric tissues in each group of rats were observed using hematoxylin-eosin (HE) staining. Enzyme linked immunosorbent assay(ELISA) was used to detect the expression of serum IL-6,interleukin-1β(IL-1β),and tumor necrosis factor alpha (TNF-α) in each rat group. The expression of B-cell lymphoma/leukemia xL (Bcl-xL) and vascular endothelial growth factor (VEGF) in the gastric tissue of rats in each group was detected by fluorescence immunohistochemistry. Western Blot was used to test the protein expression of IL-6,p-JAK2,p-STAT3,Cyclin D1 and c-Myc in the gastric tissues of rats in each group. Results Compared with the blank group,the body weight and 3-hour food intake of rats in the model group were significantly reduced(P<0.05),the gastric mucosa became thinner and incomplete. Disordered glandular arrangement and reduced glandular number were found. Goblet cells of intestinal metaplasia in gastric epithelial cells and infiltration of inflammatory cells were visible in partial area. The levels of IL-6,IL-1β and TNF-α in the rat serum were also significantly up-regulated (P<0.05),and the protein expression of IL-6,p-JAK2,p-STAT3,CyclinD1,c-Myc,Bcl-xL and VEGF in gastric tissue was obviously up-regulated(P<0.05). Compared with the model group,the body weight and 3-hour food intake of rats in medium-and high-dose of Huayu Xiaopi Decoction groups increased(P<0.05),the gastric mucosal injury were improved with different degree. Glandular arrangement was in order,intestinal metaplasia of gastric epithelial cells was improved,as well as less inflammatory cells were found. The expression of IL-6,TNF-α and IL-1β in the serum of rats remarkably decreased(P<0.05),while the protein expression of Bcl-xL,VEGF,IL-6,p-JAK2,p-STAT3,CyclinD1 and c-Myc in gastric tissue obviously down-regulated (P<0.05). Conclusion Huayu Xiaopi Decoction can effectively improve pathological damage of gastric mucosa in PLGC rats. Its mechanism maybe related to inhibiting inflammatory reaction,and suppressing cell proliferation by regulating the IL-6/JAK2/STAT3 pathway.
Huayu Xiaopi Decoctionprecancerous lesions of gastric cancerIL-6/JAK2/STAT3 pathwaycell proliferationinflammatory reactionrats