Protective Effect of Qiling Prescription on Rats with Chronic Atrophic Gastritis Combined with Gastric Intestinal Metaplasia Via PI3K/Akt Pathway

Abstract:

Objective To explore the potential mechanism of Qiling prescription in intervening in chronic atrophic gastritis with gastric intestinal metaplasia （GIM）.Method The 80 SPF-grade SD rats were randomly divided into the following eight groups （10 rats per group）： blank group， blank + Qiling prescription group， model group， high-dose Qiling prescription group， medium-dose Qiling prescription group， low-dose Qiling prescription group， folic acid group， and morodan group. Except for the blank and blank + Qiling prescription groups， the other groups underwent modeling by intragastric administration of 0.02 mol·L^-1 N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） solution combined with irregular feeding. After successful modeling， the blank and model groups were given distilled water， the blank + Qiling prescription group， and high， medium， and low-dose Qiling prescription groups were given Qiling prescription water decoction at 7.60， 15.21， 7.60， 3.80 g·kg^-1， respectively， the folic acid group was given folic acid suspension at 0.002 g·kg^-1， the morodan group was given morodan suspension at 1.40 g·kg^-1 by gavage once a day for 8 weeks. The general condition and body weight of the rats were observed during the experiment. Hematoxylin-eosin （HE） staining was performed on gastric tissues. Immunohistochemistry （IHC） was used to detect the levels of mucin 2 （MUC2） and caudal-type homeobox transcription factor 2 （CDX2） in gastric tissues. Enzyme-linked immunosorbent assay （ELISA） was used to measure the serum levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， cysteine-aspartic protease-3 （Caspase-3）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt）. Western blot analysis was performed to detect the expression and phosphorylation levels of PI3K and Akt in gastric tissues.Result Animal experiments showed that compared to the blank group， the rats in the model group had a trend of weight loss starting from week 16. Compared to the model group， high and medium doses of Qiling prescription improved the mental state and body weight of the rats. Pathological results at week 24 showed successful modeling with reduced gastric mucosal glandular cells and disordered arrangement in the model group compared to the blank group. The high and medium-dose Qiling prescription groups showed significantly fewer or absent goblet cells， indicating improved gastric mucosal pathology as compared to model group. Compared to blank group， the model group showed increased levels of MUC2 and CDX2 in gastric tissues （P<0.01）. High and medium doses of Qiling prescription significantly reduced the levels of MUC2 and CDX2 in gastric tissues compared to the model group （P<0.05，P<0.01）. Compared to the blank group， the model group had increased serum levels of IL-6， IL-1β， TNF-α， Caspase-3， PI3K， and Akt （P<0.05）. Compared with the model group， high-dose Qiling prescription significantly reduced the serum levels of IL-1β， Caspase-3， PI3K， and Akt （P<0.01）， medium-dose significantly reduced the levels of IL-6， IL-1β， TNF-α， Caspase-3， PI3K， and Akt （P<0.05，P<0.01）. Compared to the blank group， the model group showed significantly increased expression of PI3K and Akt in gastric tissues. High-dose Qiling prescription significantly inhibited Akt protein expression compared to the model group （P<0.01）.Conclusion Qiling prescription may alleviate GIM and delay inflammation-cancer transformation through multi-component， multi-target， and multi-pathway mechanisms by inhibiting the PI3K/Akt pathway， reducing the release of pro-inflammatory factors， and inhibiting gastric mucosal epithelial cell apoptosis.