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The Influence Of Fuxin Decoction On The Expression Of DAG/PKC/ERK/NF-κB In Rat’s Cardiac Fibroblasts And Its Clinical Research For The Treatment Of Chronic Heart Failure

Posted on:2018-10-06Degree:MasterType:Thesis
Country:ChinaCandidate:J J DuanFull Text:PDF
GTID:2334330518997877Subject:Internal medicine of traditional Chinese medicine
Abstract/Summary:PDF Full Text Request
Objective: Chronic congestive heart failure(CHF)is a complex clinical syndrome.A long-term ventricular hypertrophy or excessive capacity load results in a decreased myocardial contractility and insufficient ventricular output.In recent years,the research on heart failures with Chinese medicine treatment attracts more and more attention.Through many years’ effort,Professor Xue YiTao developed the Fuxin decoction,which shows effective treatment on the heart failure.In past Chen wei,Cheng Ruixue observed the influence of Fuxin decoction on the PI3 K AKT-GSK3 beta and IP3 Ca2+/CaM-CaN,GATA4 PKA/ERK,Ca N/NFAT/GATA4 signaling pathways in the myocardial tissue of heart failure rats and normal rats,and investigated the mechanism of the heart failure with signal transcription pathways through the principle of intervention.This research achieved the initial effect,and provide experimental and theoretical supports for the follow-up investigation.In this study,we observed the effect of the Fuxin decoction on DAG/PKC/ERK/NF-κB signaling pathway in secondary-generation rat cardiac fibroblasts,and evaluated the patients’ BNP level,cardiac function,TCM syndromes and quality of life.This research explores new ideas for clinics research.Methods: 1,experiments on animal: 50 healthy adult male Wistar rats were randomly and equally divided into different groups: The blank group,Fuxin decoction low,medium,high dose group and valsartan group.These rats in different groups were gavaged with saline,low,medium and high dose Fuxin Decoction and Valsartan everyday.Afte 2 weeks,the serum was separated and cryopreserved after sterilization.The cardiac fibroblasts of the heart of Wistar rats were cultured for 2-3 days after born is added to serum with medicine.With the MTT method,we determined the best intervention time and concentration gradient.The low,medium,high dose Fuxin decoction group and valsartan group are divided in 10% and 15% concentration respectively with intervention time 24 hrs and 48 hrs.With enzyme standard instrument testing analysis,we found the best concentration for both groups(15% and 15%)and intervention time of 48 hrs,and use this basis for subsequent experiments.We used the Elisa and Western-bolt method to detect the expression of DAG/PKC/ERK/NF-κB in myocardium fibroblasts.2: Clinical observation: 60 cases of CHF hospitalized patients were randomly selected and divided into control and experiment groups.The experimental group was treated with Fuxin decoction and western medicine treatment.The control group was treated with valsartan and western medicine treatment.After 6 weeks,the levels of BNP,cardiac function,TCM score,Lee’s heart failure score and quality of life score were recorded before and after treatment.A database was established with all results,expressed as ± S,and SPSS 17.0 statistical software was used for data analysis.Results:1.The experimental results:(1)the expression of DAG in myocardium fibroblasts was detected by Elisa method.The results show that the expression of DAG in Fuxin decoction group and western medicine group was lower than that in blank group with statistical difference(P<0.05).However the difference in Fuxin decoction and western medicine group is not statistically significant(P> 0.05).(2)The expression of PKCα/ERK/NF-κB in heart tissue of heart failure rats was checked by the Western blot method.The results show that PKCα was no different between two groups(P>0.05).The expression of P-PKCα is from high to low in the blank,Fuxin decoction,western medicine groups.The expression of P-PKCα is reduced in Fuxin decoction group,with statistical difference(P<0.05).The expression of P-PKCα is lowest in western medicine group compared with Fuxin decoction and blank group,with statistical difference(P<0.001).In the expression of ERK1/2 the change is not obvious(P>0.05),except from Fuxin decoction and western medicine groups.Other groups show the statistical difference(P<0.05 or P<0.01).Moreover the expression of P-ERK1/2 and NF-κB in the western medicine group was significantly higher than that in the Fuxin decoction group and the blank group(P <0.01).2 Clinical response:(1)The improvement of TCM treatment: the total efficiency after treatment is 96.7%,compared the total efficiency 73.3% in the control group,with statistical difference(P<0.05).To conclude the Fuxin decoction is better than in clinical symptoms than valsartan.(2)The Lee’s heart failure scores: two groups after treatments were significantly lower than before treatment,with a significant statistical difference(P<0.01).The efficiency of the experimental group is 77%,and the efficiency of the control group 73%,with no statistical significance(P>0.05).This indicates that the improvement in treatment of the symptoms of Lee’s heart failure is effective.(3)The level of BNP was significantly low in the two groups after treatment,and there was significant difference between the two groups(P<0.01),indicating that the level of BNP in the experimental group and the control group are significantly improved.After treatments,there was no significant difference between the two groups(P> 0.05),indicating that Fuxin decoction and valsartan in improving the level of BNP is efficacy.(4)The improvement of cardiac function: the total efficiency of the experimental group is 93.33%,and the total efficiency of the control group is 66.67%(P <0.05),indicating Fuxin decoction is better than the valsartan(5)Quality of life scores: the quality of life of patients with heart failure were significantly lower than those before treatment(P<0.01).There was significant difference between the two groups after treatment(P<0.01),indicating that the effect of Fuxin decoction group was significantly better than the valsartan group.Conclusion:1.The Fuxin decoction works in cardiac fibroblasts by the DAG/PKC/ERK/ NF-κB signaling pathway.2.The Fuxin decoction and valsartan reduce the expression of P-PKCα,ERK1/2,P-ERK1/2,the NF-κB in myocardial fibroblasts.The reduction of expression by Fuxin decoction is less than valsartan.This suggests that both of them can work through the signal pathway to inhibit fibroblast proliferation,alleviate myocardial fibrosis,the reversal of myocardial remodeling,and affect heart failure.3.The Fuxin decoction improves the symptoms of Chinese medicine,and its efficacy is better than valsartan.4.The Fuxin decoction improves the symptoms of Lee’s heart failure,and its efficacy is equivalent to valsartan.5.The Fuxin decoction significantly reduces the level of BNP in patients,and its efficacy is equivalent to valsartan.6.The Fuxin decoction significantly improves the cardiac function(NYHA),and its efficacy is better than that of valsartan.7.The Fuxin decoction significantly improves the quality of life of patients with heart failure,and its efficacy is better than valsartan.
Keywords/Search Tags:Chronic heart failure, ventricular remodeling, cardiac fibroblasts, myocardial fibrosis, the Fuxin decoction, DAG/PKC/ERK/NF-κB
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