Effects of Shu Gastric Formula modulating SCF/c-Kit pathway on gastric emptying function and interstitial cells of Cajal in rats with functional dyspepsia
Objective:To investigate the effects of Shu Gastric Formula modulating the stem cell factor(SCF)/c-Kit pathway on gastric emptying function and interstitial cells of Cajal(ICCs)in functional dyspepsia(FD)rats and molecular docking,and to analyze its mechanism of action.Methods:Thirty-two SD-grade rats,8 were ran-domly taken as the blank group,and the other 24 were randomly divided into the model group,the mosapride group,and the Shu Gastric Formula group through the multifactorial stress intervention method to establish the FD rat model.The rat gastric sinus tissue was observed by light microscope;the gastric emptying rate was detec-ted by phenol red method;the ultrastructure of rat ICCs was observed by transmission electron microscope;the content of serum SCF in the abdominal aorta of the rats was detected by ELISA;the expression of SCF and c-Kit protein in the gastric sinus tissue of the rats was detected by Western Blot;the active ingredients contained in Shu Gastric Formula were also analyzed by Western Blot;and the results were summarized.The active ingredients contained in Shu Gastric Formula were collected and screened,and molecular docking was carried out on the active ingredients with higher degree values obtained from the"active ingredient-target"topology analysis.Results:The histological structure of the stomach wall of rats in each group was complete,the epithelium of gastric mucosa was intact,the structure and arrangement of gastric glands were regular,and no obvious inflammatory cell infiltration was seen.The ultrastructure of ICCs in rats of blank group was clear,with high number,large volume,round and pike shape,more nuclei,less cytoplasm,and more mitochondria,endoplasmic reticulum and ribosomes;the ultrastructure of ICCs in rats of model group was altered,with low number,small volume,and mitochondria were swollen or vacuolated;the ultrastructure of ICCs in rats of the mosapride group and the Shu Gastric Formula group was improved,with increased number,larger volume,and improved morphology.increased,the volume became larger,and the morphology improved.Compared with the blank group,the gastric emptying rate,serum SCF content,SCF and c-Kit protein expression of rats in the model group decreased(P＜0.05);compared with the model group,the gastric emptying rate,serum SCF content,SCF and c-Kit protein expression of rats in the mosapride group and the Shu Gastric Formula group increased(P＜0.05).Formula contained 21 key active ingre-dients of Codonopsis pilosula,7 key active ingredients of Atractylodes macrocephala,22 key active ingredients of Citrus aurantium,and 2 key active ingredients of Magnolia officinalis.The molecular docking results showed that the components that docked well with the key targets were Daturilin in Codonopsis,14-acetyl-12-senecioyl-2E,8Z,10E-atractylentriol in Atractylodes macrocephala,nobiletin in Citrus aurantium,and Eucalyptol in Magnolia officinalis,the binding energies were-6.44,-6.87,-5.72,-5.66,-4.31,-5.47,-5.69,and-6.04 to SCF and c-Kit,respectively.Conclusion:Shu Gastric Formula may promote gastric motility and proliferation of ICCs and regulate gastrointestinal function in FD rats through multi-component and multi-target regulation of SCF/c-Kit pathway.
molecular dockingShu Gastric FormulaSCF/c-Kit pathwayfunctional dyspepsiainterstitial cells of Cajal
万方数据
维普
