| ObjectiveChemotherapy-induced Nausea and Vomiting(CINV)is one of the major side effects of chemotherapeutic drugs and is a high incidence in clinical.The clinical effect on delayed CINV is not very good.There is no effective radical cure in modern medicine for delayed CINV.This seriously affects the patient’s therapeutic initiative and basic physiologic physique.There are many prescriptions for the treatment of nausea and vomiting in traditional Chinese medicine,but due to its own particularity,delayed CINV is more difficult to be treated in clinical using general drugs.This study combined with the basic physique of "liver depression" and the basic treatment of nausea and vomiting in dialectical treatment of traditional Chinese Medicine.To study on the therapeutic effect of Clove,Curcuma Aromatic and Kaki Calyx Decoction of delayed CINV,Clove,Curcuma Aromatic and Kaki Calyx Decoction was used which is aimed at the basic pathogenesis of delayed CINV-"liver depression and spleen deficiency".Study the molecular mechanism of Clove,Curcuma Aromatic and Kaki Calyx Decoction in delayed CINV,through the detection of Substance P(SP)and NK-1 receptor expression in delayed CINV rat model which has given Clove,Curcuma Aromatic and Kaki Calyx Decoction.Methods48 male Wistar rats of grade SPF were purchased,and they were put in the laboratory for adaptation for one week before the experiment.In addition to the blank group,other rats were replicated the rat model of liver depression by chronic binding method.After the liver depression model was completed,the rats with unqualified weight were removed.Through the completely random in statistics,the experimental rats were divided into 6 groups,6 rats in each group.These 6 groups were blank group,model group,aprepitant group,cloves and kaki calyx Decoction group,Curcuma Aromatic group,Clove,Curcuma Aromatic and Kaki Calyx Decoction group.Rats were kaolinite adapted for 3 days and were administrated with gavage for 1 hours before modeling.Then cisplatin was injected intraperitoneally 6mg/kg,and the delayed CINV rat model was replicated.The rats were gavaged once every 12 hours after the first gavage.Cloves and kaki calyx Decoction group,Curcuma Aromatic group,Clove,Curcuma Aromatic and Kaki Calyx Decoction group were administrated by doses of 7.3,4.9,12.2g·kg-1·d-1 respectively;aprepitant group was administrated by doses of 0.0114g·kg-1·d-1 in the first day and 0.007g·kg-1·d-1 in the second and third day.Consumption of kaolin was weighed every 12 hours after the delayed CINV model was completed.Blood of venae cava inferior ileum and medulla oblongata were taken after 72 hours of delayed CINV model was completed.Detect the content of substance P with ELISA and the expression of PPTA m RNA and NK1 receptor m RNA with Real-time q PCR.Results(1)The assessment of animal models:The experimental results of 1% sucrose preference indicates that rats of model group and Curcuma Aromatic group prefer less of sucrose compared with the other groups.The results are statistically significant(P < 0.01).And compared with the blank group,the amount of kaolin fed in the model group increased(P<0.01).(2)The therapeutical effect of Clove,Curcuma Aromatic and Kaki Calyx Decoction :Compared with the model group,cloves and kaki calyx Decoction group,s,aprepitant group and Clove,Curcuma Aromatic and Kaki Calyx Decoction group,s kaolin intake decreases(P<0.01,P<0.05)and Clove,Curcuma Aromatic and Kaki Calyx Decoction group,s kaolin intake decreased significantly(P<0.01,P<0.05).Curcuma Aromatic group rats,kaolin consumption is similar with model group,s(not statistically significant).Then it increased(P<0.05).But it decreased at 36 hours after the injection of cisplatin(P<0.01).(3)The content of SP in serum,ileum and medulla which was detected by elisa: Comparedwith the blank group,SP in the serum,ileum and medulla of model group increased significantly(P<0.01).Compared with the model group,SP in the serum,ileum and medulla of aprepitant group,cloves and kaki calyx Decoction group,Clove,Curcuma Aromatic and Kaki Calyx Decoction group decreased(P<0.05,P<0.01)and reduced the most significantly in Clove,Curcuma Aromatic and Kaki Calyx Decoction group.Curcuma Aromatic group rats,expression of SP increased in the serum and ileum.There was a statistically significant compared with the blank group(P<0.01)and no statistical significance compared with the model group.Curcuma Aromatic group rats,expression of SP decreased in the medulla and there was a statistically significant compared with the model group(P<0.01).(4)Detection of the expression of PPTA m RNA in the ileum and medulla by RT-q PCR: Compared with the blank group,the expression of PPTA m RNA in the model group was significantly increased(P<0.01).Compared with the model group,the expression of PPTA m RNA in aprepitant group,cloves and kaki calyx Decoction group,Clove,Curcuma Aromatic and Kaki Calyx Decoction group decreased(P<0.05,P<0.01)and reduced the most significantly in Clove,Curcuma Aromatic and Kaki Calyx Decoction group(P<0.01).The expression of PPTA m RNA increased in the ileum of Curcuma Aromatic group and decreased in the medulla of Curcuma Aromatic group.(5)Detection of the expression of NK-1 receptor m RNA in the ileum and medulla by RT-q PCR: Compared with the blank group,the expression of NK-1 receptor m RNA in the model group was significantly increased(P<0.01).Compared with the model group,the expression of NK-1 receptor m RNA in aprepitant group,cloves and kaki calyx Decoction group,Clove,Curcuma Aromatic and Kaki Calyx Decoction group decreased(P<0.05,P<0.01)and reduced the most significantly in Clove,Curcuma Aromatic and Kaki Calyx Decoction group(P<0.01).Compared with the blank group,the expression of NK-1 receptor m RNA in the ileum of Curcuma Aromatic group was significantly increased(P<0.01).Compared with the model group,the expression of NK-1 receptor m RNA in the medulla of Curcuma Aromatic group was significantly increased(P<0.01).Conclusion(1)The delayed CINV model of liver depression and spleen deficiency was established by the combination of chronic binding method and intraperitoneal injection of cisplatin.(2)The intervention of Clove,Curcuma Aromatic and Kaki Calyx Decoction in delayed CINV has synergistic function.The treatment of Clove,Curcuma Aromatic and Kaki Calyx Decoction in vomiting of syndrome of stagnation of liver qi and spleen deficiency effects significantly.(3)The molecular mechanism of the treatment of Clove,Curcuma Aromatic and Kaki Calyx Decoction in delayed CINV is relevant to SP and NK-1 receptor.Clove,Curcuma Aromatic and Kaki Calyx Decoction control delayed CINV by reduce the expression of PPTA,NK-1 receptor and SP. |
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