Banxia Xiexin Decoction(半夏泻心汤)Treats Diabetic Gastroparesis through PLC-IP3-Ca^2+/NO-cGMP-PKG Signal Pathway

Objective To test the effect of Banxia Xiexin Decoction(半夏泻心汤,BXD)on the contraction and relaxation of gastric smooth muscle(SM)in diabetic gastroparesis(DGP)model rats,and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro.Methods Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table:control group,model group,high-,medium-and low-dose BXD groups(9.2,4.6 and 1.8 g/(kg·d),respectively),and domperidone group(10 mg/(kg·d)),10 rats per group.DGP model was established initially by a single intraperitoneal injection of streptozotocin(STZ),and was confirmed by recording gastric emptying,intestinal transport velocity and gastric myoelectric activity of rats after 2 months.Each group was treated with a corresponding drug for 4 weeks.The mRNA and protein expressions of phospholipase C(PLC),inositol triphosphate(IP3),neuronal nitric oxide synthase(nNOS),and cyclic guanosine monophosphate(cGMP)dependent protein kinase G(PKG)were detected by reverse transcription-polymerase chain reaction and Western blot,respectively,while nitric oxide(NO)and cGMP expressions were detected by enzyme-linked immunosorbent assay.Gastric tissues were obtained from rats for primary cell culture preparation.Gastric SM cells were treated with 0.8µmol/L of STZ or STZ plus 1,000,500 and 200µg/mL of BXD or STZ plus 2.5µmol/mL of domperidone for 24,48,72 or 96 h,respectively.The length of gastric SM cells and intracellular Ca^2+concentration([Ca^2+]i)before and after BXD treatment was measured.Results Compared with the model group,high-and medium-dose BXD and domperidone significantly increased the expressions of PLC,IP3,NO,nNOS,cGMP and PKG in rat’s gastric tissue(P<0.01).Gastric SM cells treated with BXD showed a time-and dose-dependent increase in cell viability(P<0.01).The treatment with high-and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased[Ca^2+]i compared with the model cells(P<0.01).Conclusions Treatment with high-and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats.The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca^2+/NO-cGMP-PKG signal pathway.