Objective To investigate the protective effect of modified Shashen Maidong Decoction in rats with chronic atrophic gastritis (CAG) and its effect on transforming growth factor-β1 (TGF-β1)/human phosphatidylinositol trihydroxy kinase (PI3K)/Akt pathway.
Methods Sixty rats were randomly divided into blank group, model group, positive control group, low-dose group and high-dose group, with 12 rats in each group. Except for the blank group, the CAG model was constructed using 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) in all groups of rats. The rats in the blank and model groups were given equal volume of saline by gavage, the rats in the positive control group were given vincristine solution by gavage, and the rats in the low-dose group and high-dose group were given 5 g/kg and 10 g/kg modified Shashen Maidong Decoction by gavage, once a day for 12 weeks. The pathological changes of gastric mucosa were observed by hematoxylin eosin (HE) staining; the contents of motilin (MTL), gastrin (Gas) and somatostatin (SS) in serum and the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in gastric tissue were detected by enzyme-linked immunosorbent assay (ELISA); the expression of proliferating cell nuclear antigen (PCNA) and B-lymphoma-2 (Bcl-2) were detected by immunohistochemistry; the real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of TGF-β1, PI3K, Akt, p-PI3K and p-Akt in gastric tissue.
Results Compared with the blank group, the gastric tissues of rats in the model group were pale, with reduced folds, thinning and edema of gastric mucosa, reduced glands, infiltration of inflammatory cells; the serum MTL level, gastric tissue IL-6 and TNF-α levels, Bcl-2 protein expression were significantly increased, while Gas, SS levels and PCNA protein expression were significantly decreased (P < 0.01); the mRNA and protein expression levels of TGF-β1, PI3K, Akt, P-PI3K and P-Akt were significantly increased (P < 0.01). Compared with the model group, with the increasing dose, the gastric tissue color in the low-dose group and the high-dose group became red and moist, with increased folds, restored structure of each layer of gastric mucosa, the regular glandular arrangement, and the better glandular atrophy; the serum MTL levels, IL-6 and TNF-α levels and Bcl-2 protein expression in gastric tissue were significantly decreased, while Gas, SS and PCNA protein expression were significantly increased (P < 0.01); the TGF-β1, PI3K, Akt, P-PI3K and P-Akt mRNA and their protein expression levels were significantly decreased (P < 0.01).
Conclusion Modified Shashen Maidong Decoction can protect gastric tissues by inhibiting the TGF-β1/PI3K/Akt pathway, up-regulating the expression of PCNA genes and down-regulating the expression of Bcl-2 genes, and inhibiting the production of inflammatory factors.
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