| Objective: Gastric cancer is characterized by high incidence,high mortality and difficult to cure,therefore,drug intervention in Gastric Precancerous Lesion(GPL)process to block the lesion process will achieve twice the result with half the effort.Sijunzi Decoction(SJZD)has the effect of nourishing qi and spleen.It is commonly used clinically for the treatment of GPL.However,the current research on the SJZD mechanisms is not detailed,and many unknown details still need to be supplemented.This study aims to systematically evaluate the efficacy of SJZD blocking GPL,and reveal its mechanism of blocking GPL by quantitative proteomics and metabolomics technology,and combine serum pharmacology to verify the efficacy mechanism.Method: Firstly,based on the pathogenesis of GPL,N-methyl-N’-nitro-Nnitrosoguanidine(MNNG)combined with an irregular diet and 40% ethanol was used to establish the animal model of GPL.Combined with the weight changes of rats,gastric tissue pathological slices HE staining and serum biochemical indexes the efficacy of the treatment of SJZD for the treatment of GPL is systematically evaluated.Secondly,quantitative proteomics technology based on stable isotope dimethyl labeling was used to explore the protein network of SJZD blocking GPL to reveal the efficacy mechanism of SJZD.At the same time,quantitative metabolomics technology was used to observe the changes of overall gastric tissue metabolic profile caused by SJZD intervention,and further confirmed the pharmacodynamic mechanism of SJZD.Then,the efficacy of SJZD at the cellular level was studied based on serum pharmacology,and the protective mechanism of SJZD human gastric mucosal epithelial cells(GES-1)(MMNG injury)was verified by CCK-8 method,Trypan blue counting,Giemsa staining,Plate cloning,Flow cytometry,Western Blot and the critical pathway inhibitor.Results: The pathological section HE staining results in the animal efficacy experiment showed that inflammatory cell infiltration occurs in the muscle layer in the GPL model group,severe intestinal metaplasia of the gland,and the treatment group of the SJZD has improved significantly.Compared with the model group,SJZD can reduce the level of LDH levels in serum,increase the level of SOD and GSH-Px,which indicates that SJZD can control inflammation and body oxidation stress,slow down the development of GPL.At the same time,there was no obvious difference in weight between the experimental group,which proves the security of SJZD applications.Quantitative proteomics found that the oxidative phosphorylation pathway downregulated in the model group(compared with the control group)was up-regulated in the SJZD treatment group(compared with the model group),indicating that SJZD may exert its efficacy through the oxidative phosphorylation pathway.Quantitative metabolomics further found that after the intervention of SJZD,the tricarboxylic acid cycle pathway upstream of oxidative phosphorylation was activated,while its parallel pathway(glycolysis pathway)was inhibited,indicating that metabolic remodeling with oxidative phosphorylation as the core was generated after SJZD intervention.The experiment of serum pharmacological experiments showed that SJZD-CS can reduce the apoptosis of GES-1 cells induced by MNNG,and the oxidative phosphorylation inhibitor can weaken the protective effect of the SJZD-CS to GES-1 cells.Conclusion: In summary,SJZD can block the GPL caused by poor dietary habits(including excessive intake of nitrite,excessive drinking,and abnormal hunger).And its mechanism depends on oxidative phosphorylation pathway,and can cause changes in energy metabolism centered on oxidative phosphorylation. |
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