| Objective:To investigate the mechanisms of Xiao-Ban-Xia Decoction（XBXD）on the role of 5-HT3Receptor and NK1 Receptor in the prevention and treatment of chemotherapy-induced nausea and vomiting.Methods:1.The chemotherapy rat pica model was established by intraperitoneal injection of 25 mg/kg 1-PBG or intravenous injection of 250 ng/kg Substance P（SP）.The amount of kaolin consumption of rats was used as an indicator of nausea and vomiting.The Wistar rats were randomly divided into normal control groups,XBXD normal control group,1-PBG model,ondansetron group,1-PBG XBXD low,middle,high dose groups,aprepitant group,SP XBXD low,middle,high dose groups.The rats were respectively administrated different drugs by means of intragastric.Kaolin consumptions,body weight,food consumptions,water consumptions were weighed and calculated once per24 h.Rats in each group were sacrificed for brain tissue detachment at the time points of24 h and 72 h after modeling.And then,the Fos positive cells counts in brainstem were detected by immunohistochemisty method.2.Using emesis-relating agonists（inclued 5-HT,2-me-5-HT,SP,and GR73632）as drugs,the inhibitory effects of ginger juice,6-gingerol,6-shogaol,and the alkaloids of Pinellia ternata on guinea pig ileum contractility in vitro were observed in organ bath.3.By NG 108-15 cells as an model system,MTT release in vitro were used to determine the optimal concentration of 6-gingerol,6-shogaol,and the alkaloids of Pinellia ternata.Application of 2-me-5-HT and GR73632 to NG108-15 cells,we examined the intracellular Ca2+levels using Fluo-8 AM dye.Results:1.Kaolin consumptions in model group were significantly increased.The high,middle and low dosages of XBXD could significantly inhibit kaolin consumptions in1-PBG or SP-treated rats.After modeling 24 h and 72 h,Fos protein expression levels of rats incresed obviously by immunohistochemisty.The high,middle and low dosages of XBXD could significantly reduce Fos protein expression levels in rats at 24h and 72h after administration.2.Ginger juice,6-gingerol,6-shogaol could inhibit guinea pig ileum spontaneous contractions,reducing the tone of contractions dose-dependently.5-HT,2-me-5-HT,SP,and GR73632 stimulated contractions of the guinea pig ileum,enhanced the tone.All the three doses（low,middle,high）of ginger and its pungent constituents could suppress the contractility,dose-dependently reduced the tone of ileum contractions stimulated by drugs;It resulted in a dose-dependently reduction in the maximum responses.Alkaloids of Pinellia ternata could inhibit guinea pig ileum spontaneous contractions,reducing the tone of contractions dose-dependently;It can antagonize the effects of four drugs on isolated guinea-pig ileum and showes a certain degree of dose dependence.3.In vitro,2-me-5-HT and GR73632 induced increase in intracellular Ca2+ concentration([Ca2+]i).The increase in[Ca2+]i was inhibited by all the three doses of 6-gingerol,6-shogaol and alkaloids of Pinellia ternata.The high dose group of the drugs and the group of positive control drug have notable inhibition effect.Conclusion:XBXD and its multi-components could improve the selective agonist induced pica of rats,which was related to the inhibition of 5-HT3 receptor and NK1 receptor.This might be one of main mechanisms of XBXD on the prevention and treatment of CINV. |
