Clinical Observations And Experimental Studies On Ventricular Remodeling Of Kuoxin Recipe On Deficiency Of Both Qi And Yin Combined Blood Stasis With Dilated Cardiomyopathy

Objective:To observe the clinical effect on ventricular remodeling of Kuoxin Recipe combined with western medicine on deficiency of both Qi and Yin combined Blood Stasis with dilated cardiomyopathy and study its mechanism,and provide a new theoretical basis and application basis for improving the prevention and treatment of dilated cardiomyopathy by traditional Chinese medicine.Methods:(1)Clinical observations:The 72 patients with dilated cardiomyopathy of both Qi and Yin combined Blood Stasis were collected and randomly divided into a treatment group and a control group with 36 cases in each group.The control group was given conventional western medicine,while the treatment group was given Kuoxin Recipe in addition to western medicine.The course of the treatment was 12 weeks.The clinical efficacy and cardiac function,TCM syndrome improvement,serum brain natriuretic peptide level(BNP),Minnesota Heart Failure Quality of Life Questionnaire(MLHFQ)score,6-minute walking distance test(6MWT),lee’s heart failure score,cardiac ultrasound,serum TGF-β 1(TGF-β 1)were evaluated before and after treatment.(2)Experimental studies:A total of 68 Wistar rats were selected,and a blank control group(normal group)was set up.The rest were intraperitoneally injected with doxorubicin for 6 weeks to establish a DCM model.Eight weeks later,according to the results of echocardiography,they were randomly divided into the model group,the captopril group and the Kuoxin Recipe group(12 in each group).We divided the Kuoxin Recipe group into three dose groups,high,middle and low.They were given intragastric administration for 4 weeks.After the treatment,the changes of left ventricular structure and cardiac function were measured by echocardiography;HE staining and Masson staining to observe the morphological changes of myocardial tissue;immunohistochemistry to observe the expression of type I collagen,type III collagen and TGF-B in rat myocardial tissue;Western-blot method was used to determine the protein expression of Bax,Bcl-2,Caspase9,JNK,p-JNK,p38 MAPK,p-p38 MAPK,ASK1,p-ASK1 in rat myocardial tissues,and to clarify the therapeutic effect of Expanding Heart Recipe on ventricular remodeling in DCM rats And further explore its possible mechanism from the perspective of cardiomyocyte apoptosis.Results:(1)Clinical observations : 1.Clinical efficacy and cardiac function: The total effective rates were 62.5% in the control group and 90.3% in the treatment group.The treatment group was significantly superior to the control group(P<0.01).2.Efficacy of TCM syndromes: After one month of treatment,the improvement of TCM syndrome score in the treatment group was better than that in the control group(P<0.01).After 3 months of treatment,the scores of TCM syndromes in both groups continued to decrease compared with 1 month after treatment(P < 0.01)and the improvement degree of the treatment group was better than that of the control group(P<0.01).The improvement of TCM clinical symptoms in the treatment group was significantly superior to the control group(P<0.01).The total effective rate of TCM clinical symptoms in the treatment group was 80.6%,and that in the control group was 46.9%,The improvement of the treatment group was better than that of the treatment group(P < 0.01).In item-by-item comparison,the treatment group was better than the control group in terms of shortness of breath,spontaneous sweating,night sweats,dry mouth,dizziness,five upset heat,dull complexion,and dark lip nails(P<0.05)Among them,spontaneous sweating,night sweats,dizziness,dull complexion,and dark lip nails had the best improvement(P<0.01).3.Serum BNP:The improvement degree of the treatment group was significantly better than that of the control group(P<0.01).4.MLHFQ score,6MWT,Lee’s heart failure score: After4 weeks,the improvement of MLHFQ score in the treatment group was significantly better than that in the control group(P <0.01).After 12 weeks of treatment,the treatment group was better than the control group in terms of MLHFQ score and6 MWT distance(P < 0.05),but there was no significant difference(P>0.05).5.Indexes of ventricular remodeling:(1)Serum TGF-β1: The improvement degree of the treatment group was significantly better than that of the control group(P<0.01).(2)Cardiac ultrasonography: The improvement on end diastolic diameter of left ventricular(LVEDD),end systolic diameter of left ventricular(LVESD),and ejection fraction of left ventricular(LVEF)in the treatment group was better than that of the control group(P<0.05);the two groups had better improvement in the thickness of the ventricular septum(There was no significant difference in IVS)and left ventricular posterior wall thickness(LVPWT)(P>0.05).(2)Exprimental studies:1.Cardiac ultrasonography:Compared with the normal group,Significant raise on LVEDD and LVESD were observed while obvious decrease on LVEF,LVFS and IVS in the model group(P<0.05).Meanwhile,almost no statistical difference was seen in LVPWT(P>0.05).Compared with the model group,all the dose groups of Kuoxin Recipe and the captopril group showed significant improvement in LVEDD,LVEF,and LVFS in rats(P<0.01),and the efficacy of Kuoxin Recipe showed a certain dose-effect relationship.LVESD in all drug intervention groups were significantly improved except in the low-dose group of Kuoxin Recipe.Almost no statistical difference was seen in IVS and LVPWT in each intervention group(P>0.05).2.Cardiac tissue morphology: Compared with the normal group,HE staining and Masson staining in the model group showed pathological changes such as cardiomyocyte hypertrophy,interstitial hyperplasia,inflammatory cell infiltration,cell arrangement disorder,etc.Compared with the model group,Each dose group of Kuoxin Recipe and captopril groups all improved.3.Immunohistochemistry:There are obvious increase on the expression of TGF-βand collagen fibers I and III in the model group when compared with the normal group.After drug intervention,all groups of Kuoxin Recipe and the captopril group decreased.The degree of improvement in the traditional Chinese medicine group Shows a certain dose-use relationship.4.Wester-Blot:There are obvious increase on the protein expression of of Bax,Caspase9,p-JNK,p-p38 and p-ASK1 in the model group when compared with the normal group.Meanwhile,Bcl-2 was significantly reduced,and the ratio of Bax/Bcl-2 was increased(P<0.01).There was no significant difference in ASK1,JNK,p38MAPK(P>0.05).Compared with the model group,the expressions of Bax,Caspase9,p-JNK,and p-ASK1 in the Kuoxin Recipe group and the captopril group were obviously reduced while Bcl-2 significantly increasing.At the same time,the ratio of Bax/Bcl-2 was decreased(P<0.01),The improvement degree of the Kuoxin Recipegroup showed a certain dose-effect relationship.There was no statistically significant difference in the improvement of p-p38 protein expression in the Kuoxin Recipe group(P>0.05).Conclusion:1.Kuoxin Recipe can effectively improve cardiac function level,decrease bnp,increase walking distance of 6 minutes and improve cardiac function of patients of both Qi and Yin combined Blood Stasis with dilated cardiomyopathy2.Kuoxin Recipe can significantly improve the clinical symptoms and quality of life of patients of both Qi and Yin combined Blood Stasis with dilated cardiomyopathy.3.Kuoxin Recipe can improve heart function by delaying ventricular remodeling in patients of both Qi and Yin combined Blood Stasis with dilated cardiomyopathy,and its mechanism is worthy of further study.4.Kuoxin Recipe can significantly improve the cardiac function and ventricular remodeling of rats with dilated cardiomyopathy induced by doxorubicin.5.Kuoxin Recipe can delay ventricular remodeling by improving myocardial apoptosis in rats with dilated cardiomyopathy,and its mechanism may be inhibition of ASK1-JNK pathway.