| The heart is an organ with high function,high energy consumption,and low energy storage,whose supply of energy and nutrients is critical.In patients with heart failure,the systemic circulation congestion is very common,among which the edema and congestion in the gastrointestinal mucosa is very significant.It will affect the patient's feeding function,and then lead to the organism's poor nutrition absorption.The absorbing obstacle of nutrients will greatly affect the myocardial energy metabolism,eventually leading to myocardial atrophy and accelerating the malignant development of heart failure.This phenomenon belongs to "cardiogenic malnutrition".The treatment of cardiogenic malnutrition is clinically contradictory.By increasing feeding and supplementing enteral nutrition,the patient's absorption will be very poor;by parenteral supplementation,it is easy toaggravate the heart preload and lead toincreasing heart failure and sudden death.Therefore,how to interrupt the vicious cycle chain is of great importance in the prevention and treatment of cardiogenic malnutrition.The "Qi" in the traditional Chinese medicine and the "energy" of modern biologyhave certain similarities in concept.Both of them are the drives force for maintaining the lif e activities of the organism.It is founded from the previous clinical observations that p atients with cardiogenic malnutrition are mostly accompanied by manifestations of Qi deficiency syndrome,such as palpitation shortness of breath,tiredness,weak tongue,thin p ulse,etc.The intervention of cardiogenic malnutrition from the perspective of the combi nation of "Qi" in TCM theory and the understanding of "energy" in contemporarybiolo gy theory may be a further exploration in medical practice.On the basis of previous researches,this thesis is guided by the theories of the traditional Chinese medicine,such as "the heart dominates blood circulation and vessels","Qi is the mother of blood","the blood is handsome for Qi",etc.It takes the combinationof prevention and treatment as the goal,takes the energy metabolism of the heart as the entry point,selects the classical representative--Buyang Huanwu Decoction(have the function of benefiting Qi and activating blood)as the prescription,and conducts the qualitative and quantitative analysis with the help of many objective indicators,such as mitochondria,PPAR?/PGC-1?signaling pathway,etc.From organs,tissues,cells and molecular levels,it observes the characteristics and laws of myocardial energy metabolism disorder in rats with cardiogenic dystrophy,and explores the intervention effect and drug target of the Yiqihuoxue method on cardiogenic malnutrition.Meanwhile,it analyzes the distribution rules and characteristics of TCM syndromes of cardiogenic malnutrition,andexplores the characteristics of TCM syndromes of the disease initially,which provides thebasis for the prevention and treatment of cardiogenic malnutrition by TCM prescriptions.It hascertain practical significance to improve its quality of life,reduce medical expenses,anddelay the progression of heart failure.This thesis consists of two parts: the experimental research and the clinical research.Research ObjectiveThe first part of this research takes myocardial energy metabolism as the entry point,explores the effect of the Yiqihuoxue method on ?-myosin heavy chain(?-MHC),?-myosin heavy chain(?-MHC),mitochondrial-related protein 1(Drp1 m RNA),mitochondrial ultrastructure and PPAR?/PGC-1? signaling pathway in rats with cardiogenic dystrophy,verifies the hypothesis that the Yiqihuoxue method can interfere with cardiogenicmalnutrition,and provides a certain basis for the research on the traditional Chinese medicine in the treatment of cardiogenic malnutrition.The second part of this research applies the clinical epidemiological investigation method to analyze,summarize,and comb the distribution rules and characteristics of TCM syndromes in patients with cardiogenicmalnutrition so as to provide a certain reference for further clarifying this disease's syndrome Differentiation,syndrome Differentiation,and the evolution law of the disease syndrome.Research MethodsIn the first part of this research,36 SD male rats were designed to establish a model of cardiogenic dystrophy.Rats were divided into 4 groups as follows:(1)Sham operation group;(2)Model group;(3)Chinese medicine group;(4)Western medicine group.The Chinese medicine group and the western medicine group were given Fuyang Huanwu Decoction12.72g/(kg.d)and metoprolol tartrate 0.0045g/(kg.d)respectively.The sham operation group and the model control group were given the same metered demonized water.Each group was intragastrically administered once a day for a total of 8 weeks of intervention,and the corresponding indicators were observed.Myocardial ?-MHC,?-MHC,and Drp1 m RNA were measured by real-time fluorescence quantitative(RT-PCR)method.Myocardium and mitochondrial ultrastructure were respected by transmission electron microscopy.The method of Enzyme-linked Immunosorbent Assay(ELISA)was adoptedto determine the contents of Adenosine Monophosphate(AMP),Adenosine Diphosphate(ADP),Adenosine Triphosphate(ATP)in the monophosphate of rat peripheral blood;the Western blot was adopted to determine the protein expression level of Adenosine 5'-Monophosphate(AMP)-activated Protein Kinase(AMPK),Peroxisome Proliferators-activated Receptors Alpha(PPAR?),and PPAR? co-activator 1?(Peroxisome Proliferator-activated Receptor-?coactivator-1?,PGC-1?)in rats' myocardial tissue.The second part of this research draws on the epidemiological cross-sectional research design method,designs the TCM syndrome collection scale for cardiogenic malnutrition,collects TCM syndromes,four diagnostic information,and epidemiological distribution data of the patients,and summarizes them.Research Results(1)Compared with the sham operation group,the body weight and serum albumincontent of the model group were significantly decreased(P<0.01),and the weight of the heart was significantly increased(P<0.01).Compared with the model group,the weight of the rats in the Chinese medicine group and the western medicine group were serum white.The protein content was significantly increased(P<0.01),and the weightof the heart was significantly reduced(P<0.01).(2)Compared with the sham operation group,the expression of ?-MHC m RNA in the model group decreased(P<0.05),and the expression of ?-MHC m RNA and Drp1 m RNA increased(P<0.05).Compared with the model group,the expression of ?-MHC m RNA in the Chinese medicine group increased(P<0.05),the expression levels of ?-MHCm RNA and Drp1 m RNA in Chinese medicine group and western medicine group were all decreased(P<0.05).(3)Compared with the sham operation group,the levels of AMP and ADP in themodel group were significantly increased,and the ATP content was significantly decreased(P<0.01,P<0.05);compared with the model group,the AMP content in the Chinese medicine group was significantly lower(P<0.01).The ADP content decreased(P<0.05),the ATP content increased,the AMP content of the western medicine group decreased significantly(P<0.01),the ADP content decreased,and the ATP content increased.(4)Transmission electron microscopy showed that,compared with the sham operation gr oup,the myocardial filament structure of the model group was significantly disordered,t he typical sarcomere structure disappeared,the mitochondrial ultra fine knot was obviou sly swollen,the vacuole was deformed,and the number decreased.Compared with the model group,the myocardial structure of the rats in the traditional Chinese medicine gr oup and the western medicine group was significantly improved;their muscle sections were arranged neatly;the morphology of the mitochondria was significantly improved;th e number was significantly higher than that before.(5)Compared with the sham operation group,the expression of AMPK protein in each group was not statistically different.The expression of PPAR? and PGC-1? protein in the model group was significantly decreased(P<0.05).Compared with the model group,the expression levels of PPAR? and PGC-1? in the Chinese medicine group and the western medicine group were significantly increased(P<0.05).(6)In patients with cardiogenic malnutrition,the core syndrome of Chinese medicine(frequency was greater than 50%)was followed by low voice,distress,edema,palpitations,chest tightness,dry throat,insomnia,dizziness,fatigue,long-term asthma.(7)Among the 70 cases of cardiogenic malnutrition investigated,TCM syndrome differe ntiation was more common in Qi-Blood deficiency and Qi-Yin deficiency.The remainin g syndromes were Heart-Kidney Yin deficiency,Heart-Qi deficiency,Heart-Yin deficienc y and heart palpitations resistance,and sputum resistance.(8)In the types of malnutrition in patients with cardiogenic malnutrition,Protein-energy malnutrition(hypoproteinemia)accounted for 92.9%,micronutrients(iron deficiency ane mia)accounted for 58.6%,and patients of both types accounted for 51.4%;Through co mprehensive nutrition evaluation,there were 9 people with mild malnutrition,53 with m oderate malnutrition,and 8 with severe malnutrition.Conclusion(1)The Buyang Huanwu Decoction can improve myocardial and mitochondrial ultrastructure,increase mitochondrial oxidative phosphorylation level,and maintain energy metabolism in failing myocardium.(2)The Buyang Huanwu Decoction may inhibit myocardial remodeling and protect myocardial tissue by inhibiting the conversion of ?-MHC to ?-MHC and inhibiting the isolation of Drp1 m RNA from mitochondria.(3)The Buyang Huanwu Decoction may improve the energy metabolism of the failing heart and delay the progression of heart failure by up-regulating the expression of PPAR?/PGC-1?signaling pathway.(4)Most of the patients with cardiogenic malnutrition are in moderate malnutrition,and there are no significant differences between men and women;the principal types of malnutrition are protein--malnutrition in energy nutrition and micronutrient.(5)The core syndromes of cardiogenic malnutrition are low sonic fatigue,edema palpitations,dry throat and thirst,fatigue and fatigue,etc.Qi-blood deficiency,Qi-yin deficiency are common syndromes of cardiogenic malnutrition.(6)Most patients with cardiogenic malnutrition are associated with cardiogenic and dystrophic edema,which may lead to abnormal body mass index and affect the judgment of individual nutritional indicators.Therefore,the application of comprehensive nutrition assessment tools is more objective and accurate. |
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