Effect Of Hewei Decotion On SCF-Kit Signaling Pathway In Gastric Antrum Of Rats Model With Diabetic Gastroparesis

Diabetic gastroparesis (DGP) which is one of the common complications of diabetes seriously affects the patient’s quality of life.Its pathogenesis has not been fully elucidated. Many studies showed that interstitial cells of Cajal (ICC) abnormlities was correlated with DGP.Stem cell factor (SCF) is the main ligand of Kit, a receptor tyrosine kinase and also the surface maker of ICC.SCF-Kit signaling pathway is very important for the differentiation, development, proliferation and phenotype maintenance of ICC.Prokinetic agents show a definite effect on DGP. While we expect to fundamentally improve the basis of the disease and achieve the desired therapeutic purposes according to the pathogenesis of DGP.Hewei Decotion (composed of Radix Rehmanniae, Radix Ophiopogonis, Polygonatum Odoratum, Radix Glehniae, Rhizoma Atractylodis Macrocephalae, Bergamot and Semen Raphani) based on the pathogenesis of stomach-yin deficiency and spleen-qi deficiency has achieved a good curative effect in the clinical treatment but its specific mechanism has not been elucidated.Our previous studies found that Hewei Decotion could improve gastric motility, gastric blood flow and the quantity of ICC in DGP rats.However, whether Hewei Decotion improves the number and maintains function of ICC by SCF-Kit signaling pathway so as to improve gastric emptying is yet to be proved by further experiment.Purpose:To investigate the role of SCF-Kit signaling pathway in the damage of ICC in gastric antrum of DGP rats and the therapeutic mechanism of Hewei Decotion.Methods:Adult male Sprague-Dawley (SD) rats were divided randomly into normal control group, model group, high dose of Hewei Decotion group, low dose of Hewei Decotion group and Domperidone group.DGP model rats were made by once celiac Streptozocin (STZ) injection.Gastric lavage method was used to administer the tradional Chinese medicine decotion of Hewei and Domperidone suspension in corresponding amount respectively.Equal amount of normal saline was administrated to the normal group and model group.After six weeks, gastric emptying rate was determined by Phenol red gavage experiment.The quantity of ICC in the gastric antrum was determined by immunohitochemistry. Western blot was used to detect c-kit and membrane-bound stem cell factor (mSCF) protein expression level in the gastric tissue.The soluble stem cell factor (sSCF) level in serum was detected by ELISA.Results:Compared with normal group, the gastric emptying rate, the quantity of ICC, c-kit and mSCF protein expression level in the gastric tissue and sSCF level in serum were significantly lower in model group (P<0.01). Compared with model group, the gastric emptying rate, the quantity of ICC, c-kit and mSCF protein expression level in the gastric tissue and sSCF level in serum were significantly higher in each therapy group (P<0.05), and with the increase of the concentration of traditional Chinese medicine, the improvement is more obvious.High dose of Hewei Decotion group has therapeutic equivalence with Domperidone group.Conclusion:Hewei Decotion can improve gastric pacing function and gastric motility by up-regulating SCF-Kit signaling pathway to regulate the quantity of ICC in DGP rats.