Hongqi(红芪)Polysaccharide Regulates Calcium Homeostasis and Energy Metabolism in Rat Model of Diabetic Gastroparesis via cAMP/PKA Signaling Pathway
Objective:To explore the mechanism of Hongqi(红芪)polysaccharide(HPS)in regulating the calcium homeostasis and energy metab-olism in the rat model of diabetic gastroparesis(DGP).Methods:Sixty-two male Wistar rats were randomized into a blank group(n=12)and a modeling group(n=50).The DGP model was established by multiple injections of streptozotocin combined with feeding with an irregu-lar diet.The modeled rats were randomized into model control,mosapride(1.35 mg/kg),and HPS(200,100,and 50 mg/kg)groups.The rats in each group were administrated with corresponding drugs by gavage,while those in the blank and model control groups were administra-ted with equal volumes of pure water by gavage.The general conditions of rats were observed,and the body mass,random blood glucose,and gastric emptying rate were measured.Hematoxylin-eosin staining was conducted to observe the pathological changes of the gastric antrum tis-sue in rats.Enzyme-linked immunosorbent assay was employed to measure the levels of ATP,Na+-K+ATPase,Ca2+-Mg2+ATPase,and calcium ion(Ca2+)in the gastric antrum tissue.Immunohistochemistry and Western blotting were respectively employed to detect the distribution and determine the protein levels of cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),calmodulin-dependent protein kinase Ⅱ(CaMKⅡ),and their phosphorylated forms in the gastric antrum tissue.Results:Compared with the blank group,the model control group showed decreased body mass and gastric emptying rate,lowered levels of ATP,Na+-K+ATPase,and Ca2+-Mg2+ATPase,down-regulated protein levels of cAMP and PKA,elevated blood glucose and Ca2+levels,and up-regulated protein levels of CaMKⅡ and its phosphorylated form in the gastric antrum tissue(P<0.01).Compared with the model control group,drug interventions increased the body weight and gastric emptying rate,elevated the levels of ATP,Na+-K+ATPase,and Ca2+-Mg2+ATPase,up-regulated the protein levels of cAMP and PKA,lowered the blood glucose and Ca2+levels,and down-regulated the protein levels of CaMKⅡ and its phosphorylated form in the gastric antrum tissue(P<0.05 or P<0.01).Conclusion:HPS can regulate calcium homeostasis and promote energy metabolism in DGP rats by up-regulating the expression of cAMP/PKA signaling pathway and inhibiting CaMKⅡ activity.