| ObjectiveWe evaluate the clinical efficacy of Jianpibuxue formula on Gastrointestinal reactions and myelosuppression after chemotherapy in non-small cell lung cancer(NSCLC),aiming to seek a safe,effective and convenient comprehensive treatment of Chinese and Western medicine,and to improve the quality of life of patients with chemotherapy.To investigate the mechanism of the vomiting prevention effect of Jianpibuxue formula,we detected the expression of Ghrelin in plasma,the expression of VIP mRNA in brain tissue and the expression of VIP mRNA in Gastric tissue by laboratory modeling.To explore mechanism of Jianpibuxue formula on improving the spleen hematopoietic function and reducing the role of bone marrow suppression after chemotherapy,we detected the expression of CD34 in spleen tissue after cyclophosphamide treatment.Methods60 cases of chemotherapy patients with non-small cell lung cancer(GP)were selected as the subjects with randomized and controlled principles.The WHO anti-cancer drugs in acute and subacute toxicity reaction grading standards,the evaluation scale of abdominal fullness and distention(TCM),the evaluation scale of leukopenia(TCM),Symptom rating scale of primary lung cancer and lung cancer survival quality measurement scale(FACT-L Chinese 4.0)were used as a therapeutic index to evaluate the curative effect on the chemotherapy-induced Gastrointestinal reaction and myelosuppression,and provided a clinical evidence for popularization and application.To study the mechanism of effect of Jianpibuxue formula on reducing nausea and vomiting and myelosuppression after chemotherapy,we established the cisplatin chemotherapy mice model to observe the effect of Jianpibuxue formula on the whole situation of chemotherapy mice(including general condition,body weight and feeding water),and estimated the content of plasma Ghrelin,the mRNA expression of Gas in brain tissue and the mRNA expression of VIP in the Gastric tissue.We also established the cyclophosphamide chemotherapy mice model to detect expression of CD34 in the spleen tissue.Results1.Result for Clinical StudyWe observed the digestive tract reaction for 15 days according to WHO Anti-cancer Drugs in Acute and Subacute Toxicity Reaction Grading Standards.The result showed that the incidences and degrees of nausea and vomiting,appetite loss of the control group were higher than the treatment group,the differences were statistically significant(P<0.05),while the incidences and degrees of diarrhea,constipation,and oral ulcer of the two groups were compared with no statistically significant difference(P>0.05).We observed abdominal fullness and distention symptom for 15 days according to the Evaluation Scale of Abdominal Fullness and Distention(TCM).The result showed that the scores of treatment group were lower than the control group at the corresponding time points(D2,D8,D15),the difference was statistically significant(P<0.05).The interaction of timing and grouping shows that the variation tendency of scores between the treatment group and control group are different with time-varying(P<0.05).Choosing the score of D2 and D8 to evaluate the curative with traditional Chinese medicine.It shows that the total effective rate of the treatment group was 96.7%,while the control group was 93.3%(P>0.05).The effect of distribution in the two groups was compared with statistically significant difference(P<0.05).We observed leukopenia symptom for 21 days according to the Evaluation Scale of Leukopenia(TCM),compared with the scores of D2,D8,D15 and D21.The result showed that the scores of treatment group were lower than the control group at the corresponding time points(D2,D8,D15),the difference was statistically significant(P<0.05).The interaction of timing and grouping shows that the variation tendency of scores between the treatment group and control group are different with time-varying(P<0.05).Choosing the score of D8 and D15 to evaluate the curative with traditional Chinese medicine.The total effective rate of the treatment group was 96.7%,while the control group was 73.3%(P<0.05).The effect of distribution in the two groups was compared with no statistically significant difference(P<0.05).We choose 4 time-points(before treatment,D8,D15,D21)to observe and compare the variation of white blood cells,neutrophils,red blood cells,hemoglobin and platelet between the treatment group and control group according to the WHO Anti-cancer Drugs in Acute and Subacute Toxicity Reaction Grading Standards.Compare the count of white blood cells,neutrophils,red blood cells,hemoglobin and platelet between the treatment group and control group in D8 and D15,we found that the treatment group was obviously higher than control group(P<0.05).The red blood cells and hemoglobin of treatment group and control group had no obviously variation during observation,and the difference was not statistically significant at the same time-point(P>0.05).Compared with the incidence and decline degree of red blood cells,hemoglobin and platelet between the treatment group and control group,the differences were not statistically significant(P>0.05).We compared the variation with clinical symptoms of TCM before treatment(D1)and after it(D21),according to Symptom Rating Scale of Primary Lung Cancer.The result shows that both the scores of the treatment group and control group are decreased(P<0.05),but more obviously with the treatment group,and the difference was statistically significant with control group(P<0.05).We compared the variation with the quality of life before treatment(D1)and after it(D21),according to Lung Cancer Survival Quality Measurement Scale(FACT-L Chinese 4.0).The result shows that the score of two groups were lower than the score which is before treatment in physiology,function,emotion and additional attention(P<0.05).The score of the treatment group was higher than control group after treatment(P<0.05).There was no difference in the score of two groups before and after treatment,and was no statistically significant in the field of society or family(P>0.05).We compared the variation of Karnofsky score and weight before and after treatment with two groups.It shows that the improvement rate and degree of improvement for treatment group were obviously better and higher than the control group after treated(P<0.05).Compared with weight of two groups,there was no statistical difference(P>0.05).We monitored ECG and hepatorenal function of all patients before and after treatment(ALT,AST,BUN,CREA).The result shows that the ECG and hepatorenal function of patients in two groups had no obviously abnormal variation.2.Result of Animal ExperimentWe observed the overall situation(included general situation,weight and intake of water and food,and so on)of mice in high dose group,middle dose group and low dose group after using cisplatin for 72 hours,and found that the groups of which used Chinese medicine were all better than model group.The overall situation of high dose group is the best of all groups,no differences with the blank group,secondly is middle dose group and low dose group.After treated with Cisplatin,the serum Ghrelin in model group was obviously decreased.The expression of brain Gas mRNA and stomach VIP mRNA obviously increased,compared with blank group was different in statistic(P<0.05).The serum Ghrelin of high dose group and middle dose group with Chinese medicine were obviously higher than model group,while low dose group in Chinese medicine compared with model group,had no differences in statistic(P>0.05).The expression of brain Gas mRNA and stomach VIP mRNA with Chinese medicine were obviously lower than model group(P<0.05).After treated with cyclophosphamide,the expression for CD34 in spleen of model group was obviously increased(compared with blank group,P<0.05),while middle dose group and low dose group were obviously increased than model group.ConclusionClinical study results suggest that: Jianpibuxue formula sides with 5-HT3 receptor antagonist drugs,can effectively reduce the nausea and vomiting,fullness,loss of appetite and other symptoms in non-small cell lung cancer patients after chemotherapy;prevent white blood cells,neutrophils,platelets declining,and enhance the hematopoietic function of chemotherapy patients;reduce the clinical symptoms of patients with lung cancer,improve their physiological status,functional status,emotional status,additional attention and other areas of quality of life.Suggesting that Jianpibuxue formula has synergistic effect on the treatment of Gastrointestinal reactions after chemotherapy and myelosuppression,and improved the quality of life during chemotherapy in lung cancer patients.Also further verified the "spleen lost health transport,qi and blood deficiency" is after chemotherapy,Gastrointestinal reactions,myelosuppression of one of the basic pathogenesis.Strengthen the spleen and Replenish blood as the basic principle of treatment can achieve a certain effect,clinical worthy of promotion and application.The results of animal experiment showed that Jianpibuxue Formula can increase appetite and improve the general situation to the mice of which used cisplatin for chemotherapy.The high dose group and middle douse group for Jianpibuxue Formula can increase the serum Ghrelinof mice with Cisplatin,while high dose group,middle dose group and low dose group can decrease the expression of brain Gas mRNA and stomach VIP mRNA,shows that the mechanical of Jianpibuxue Formula in decreasing the chemotherapy-induced nausea and vomiting probably was inhibit the expression of brain Gas mRNA and stomach VIP mRNA by promoting Ghrelin secretion,thus decreasing the hurt to Gastrointestinal mucosa from chemotherapeutics,promoting Gastrointestinal motility and speeding up Gastric emptying.Jianpibuxue Formula can increase the spleen-weight of mice with cyclophosphamide,the spleen index of mice and the expression for CD34 in spleen,suggested the mechanical of decreasing the chemotherapy-induced myelosuppression with Jianpibuxue Formula might be connected with the spleen volume recovery and the number of hematopoietic stem cells in spleen,thereby improving the function of hematopoiesis in the spleen.After cisplatin chemotherapy,some mice were mentally retarded,low response,limb curled up,intake reduction,weight loss,dry hair off and other symptoms.It happens the most obvious in the model group.The plasma Ghrelin content in the model group was significantly decreased while the expression of Gas mRNA in brain and the expression of VIP mRNA in gastric tissue were significantly enhanced.Combined with the general situation of mice and Gastrointestinal hormones suggest that after cisplatin chemotherapy the mouse may be "spleen deficiency" as the main symptom.It's the same as clinical treatment of patients with Gastrointestinal reactions after chemotherapy,which shows deficiency of the spleen qi,lost of health transport.Jianpibuxue Formula can increase the appetite of mice with cyclophosphamide,and improve the general situation by regulating the mouse plasma Ghrelin content,Expression of Gas mRNA in brain tissue and VIP mRNA in gastric tissue.Suggesting that may improve the cisplatin chemotherapy mice "spleen deficiency" symptom. |
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