| ObjectiveThrough experimental research and clinical trials,the protective effect of Qidongyixin Liquid on cardiotoxicity after chemotherapy in patients with malignant tumors was thoroughly explored,the protective mechanism and material basis of Qidongyixin Liquid,and the improvement effect of Qi deficiency syndrome after chemotherapy were explored.The theory of traditional Chinese medicine for the prevention and treatment of cardiotoxicity of chemotherapeutic drugs and the clinical application of Chinese medicine intervention in cardiotoxicity of chemotherapy drugs.MethodExperiment researchExperiment 1:90 male BALB/c mice were randomly divided into 6 groups:control group,adriamycin model group,dexrazoxane group,Qidongyixin liquid 10ml/kg dose group(clinical Effective doses),Qidongyixin liquid 25ml/kg dose group,Qidongyixin liquid 50ml/kg dose group,15 in each group.Control group and adriamycin model group were given distilled water by gavage,Qidongyixin liquid group were given different doses of Qidongyixin liquid.Seven days after the administration,dexrazoxane group was intraperitoneally injected with dexrazoxane 200 mg/kg.One hour later,except for the control group,the other 5 groups were intraperitoneally injected with 15 mg/kg adriamycin and maintained for 14 days.Observation indicators:(1)Heart function-related indicators:echocardiography,electrocardiogram,myocardial enzyme levels.(2)Cardiomyocyte injury and apoptosis-related indicators:HE staining,TUNEL apoptosis detection,westernblot analysis of myocardial apoptosis protein caspase 3/9,Bcl-2,and Bax.Experiment 2:90 S180 tumor-bearing mice were randomly divided into 6 groups:control group,adriamycin group(adriamycin 1 mg/kg),Qidongyixin liquid 10ml/kg dose combined with Adriamycin group,Qidongyixin liquid 25ml/kg dose combined with adriamycin group,Qidongyixin liquid 50ml/kg dose combined with adriamycin group,dexrazoxane group(dexrazoxane 200mg/kg),15 in each group.The control group and adriamycin group were given water by gavage;Qidongyixin liquid was given by gavage with different doses of Qidongyixin liquid groups;dexrazoxane group was given intraperitoneal injection of dexrazoxane 200mg/kg.Drugs were continued for 7 consecutive days and after that adriamycin was injected for 12 days.Observation indexes:(1)Heart function-related indicators:echocardiography,electrocardiogram,myocardial enzyme levels.(2)Cardiomyocyte injury and apoptosis-related indicators:HE staining,TUNEL apoptosis detection,westernblot analysis of myocardial apoptosis protein caspase 3/9,Bcl-2,and Bax.(1)Related indicators of tumor inhibition rate:the length of the long axis and the length of the short axis and tumor weight of the mice in each group were detected.Clinical TrailA central randomized controlled,multi-center clinical trial was used to randomize patients with heart-qi deficiency following chemotherapy for malignant tumors that met the inclusion criteria.The patients were randomly divided into Qidongyixin liquid group and Shengmai Yin group.Intervention for 14 days statistically related treatment results.To compare the symptoms and signs associated with heart-qi deficiency syndrome at different visit points and observe the effect of Qidongyixin liquid on related indicators of heart-qi deficiency after chemotherapy for malignancy,and to discuss the effect of Qidongyixin liquid on improvement of heart-qi deficiency after chemotherapy for malignant tumors.ResultsExperimental research:(1)Heart Function Index Study Results.First experiment.Echocardiography:Compared with the adriamycin model group,the Qidongyixin liquid group dose-dependently increased the left ventricular transverse axis shortening rate,cardiac ejection fraction,diastolic left ventricular volume(p<0.01);the level of the heart function was higher in the dexrazoxane group than in the model group(p<0.01).Electrocardiogram:Compared with the adriamycin model group,the Qidongyixin liquid group dose-dependently reduced the ST segment of the electrocardiogram and increased the heart rate(p<0.01);The difference was statistically significant(p<0.05)between the 50 ml/kg group and the dexrazoxane group.Myocardial enzyme:Compared with the adriamycin model group,Qidongyixin liquid dose-dependently reduced the serum LDH,CK,AST test values(p<0.01);The decrease of myocardial enzyme activity was better than that of Qidongyixin liquid in each dose group,and the difference was statistically significant(p<0.01).Second experiment:Echocardiography:Compared with the adriamycin model group,the Qidongyixin liquid group dose-dependently increased the left ventricular transverse axis shortening rate,cardiac ejection fraction,diastolic left ventricular volume(p<0.01);the level of the heart function was higher in the dexrazoxane group than in the model group(p<0.05).Electrocardiogram:Compared with the adriamycin model group,the Qidongyixin liquid group dose-dependently reduced the ST segment of the electrocardiogram(p<0.01).Myocardial enzyme:Qidongyixin liquid dose-dependently reduced the serum LDH,CK,AST test values(p<0.01);The effect of reduction LDH and CK was better than that of dexrazoxane group by Qidongyixin liquid 50ml/kg group(p<0.01).(2)Cardiomyocyte Injury and Apoptosis Index Results.TUNEL assay:adriamycin can induce apoptosis in cardiomyocytes of normal mice/tumor-bearing mice,and Qidongyixin liquid dose-dependently reduces the number of cardiomyocyte apoptosis.Westernblot analysis:The expression of apoptotic caspase 3/9 was significantly increased in the adriamycin group,the expression of pro-apoptotic protein Bax was increased,and the expression of anti-apoptotic protein Bcl-2 was decreased;Qidongyixin liquid can reduce apoptosis in a dose-dependent manner.(3)Tumor inhibition study results:The lengths of the long axis and short axis of the tumor in the adriamycin group were significantly decreased,and the tumor weight was significantly decreased.There was a statistically significant difference compared with the control group(P<0.01).The combination of Qidongyixin Liquid 25ml/kg with adriamycin and Qidongyixin Liquid 50ml/kg combined with adriamycin significantly reduced the tumor's long axis,short axis,and tumor weight.Compared with the control group,there was a statistically significant difference between the adriamycin group(P<0.01).Clinical research:(1)Comparison results of single symptom scores in the experimental group:The experimental group had improved palpitation,fatigue,shortness of breath,sweating,and insomnia after medication.Symptoms of fatigue symptoms:There was a statistically significant difference between visit point 1 and follow-up visit points and baseline(P<0.01);statistics of sweating,insomnia symptoms scores,visit points 2 and visit points 3 were comparable to baseline,and the differences were statistically significant.Significance(P<0.01);statistics of single symptom scores of palpitations and shortness of breath,and comparison of visit points three with baselinet(P<0.01).(2)Comparison results of single symptom scores among groups.Improvement of single symptom scores results:Improvement of single symptom scores of shortness of breath,fatigue,and sweating.The test group was significantly better than the control group,(P<0.01).Insomnia symptoms score improvement,the test group was better than the control group(P<0.05);the improvement of palpitation scores,there was no statistical difference between the two groups(P>0.05).Single symptom effectiveness study results:fatigue,sweating,the effectiveness of the test group was significantly better than the control group(P<0.01);shortness of breath,insomnia,the test group was better than the control group(P<0.05);There was no statistical difference between the two groups in palpitations(P>0.05).(3)Comparison results of total score indicators between groups:There was no significant difference in total scores between baseline and visit points between the two groups(P>0.05);there was no significant difference in improvement of total scores between the two groups(P>0.05).(4)Analysis of Linear Trends of Symptom Score in Two Groups:The scores of the individual symptoms and the total scores of the two groups,and the visit time as the change factor,all showed a significant downward trend(P<0.01);Shortness of breath,changes in fatigue strength curve(P<0.05);heart palpitations,sweating,insomnia integration curve,the amount of comparison between groups(P>0.05);The total score change curve of the two groups There was statistical difference between the two groups(P<0.01).(5)Safety Index:Before and after the safety index of the test group was compared,there was no statistical difference(P>0.05).ConclusionThe important conclusions obtained in this study are as follows:(1)Experiental research:Qidongyixin Liquid has a synergistic and attenuating effect on Adriamycin,it can dose-dependently improve cardiac toxicity associated with adriamycin-related cardiac dysfunction,ECG abnormalities,elevated myocardial enzymes,myocardial cells Injury and apoptosis;adriamycin 50ml/kg group is basically consistent with dexrazoxane in the cardioprotective effect of adriamycin;Qidongyixin Liquid combined with adriamycin has a synergistic anti-tumor effect and is superior to adriamycin alone.(2)Clinical trail:Qidongyixin Liquid can effectively improve the cardiotoxicity of chemotherapeutic drugs related to heart qi deficiency,the most effective and rapid improvement of fatigue symptoms,visible improvement effect within 5 days;shortness of breath,sweating,Insomnia and heart palpitations all have significant effects.Qidongyixin Liquid has potential improvement effect on the platelet count after chemotherapy. |
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