Study On Interfere In Congestive Heart Failure After Myocardial Infarct By Yiqi Wenyang Huoxuefang

First part theoretical researchThe congestive heart failure (CHF) belongs to the Traditional Chinese Medicine (TCM) as "the palpitation", " syndrome of Yin ", "the syndrome of wheeze", "dropsy" and so on, in all previous Chinese medicine literature, discuss the aetioligy and pathogenesis of the CHF quite a lot. "Plain Question·Nidiaolun" said: "Can not to lie, lies then wheeze, is encroached by water". "Plain Question·Zangqifashilun" said: "The nephrosis, the abdomen large and dropsy in anticnemion, gasping, coughing and feeling of heaviness in the body, perspiration in sleeping and hate wind". Consider: "dropsy", "gasping and coughing", "Can not to lie", are due to water exudes result of deficiency of the kidney. "Blood evidence Discusses" thought: "water and blood are interrelated", "water sick relate to blood, blood sick relate to water, to regulates water is to regulates blood, vice versa." This has expounded the relationship about the blood and the water in morbility and treatment, guiding later generation in treatment and differentiation of symptoms and signs.TCM has a long history and the good curative effect in treating "dropsy", "gasping", "coughs", "can not to lie" and so on. In recent years, along with the development of research method, through unifies differentiate disease with differentiate symptoms and sign, the gnosia to CHF in aetiology and pathogenesis of TCM is more deeply and also consonance. This disease is deficiency in root and excess in appearance, deficiency of yang and Qi, excess of blood stasis, water detention, phlegm block. The sick entrails is heart, implicate liver, spleen, kidney and so on. Deficiency and excess affect to each other, becomes the cause and effect for the other. Heart sick, but relations to the lung, spleen, kidney and liver closely. In the aspect of treatment, TCM emphasized strictly on the pathogenesis, differentiation of syndromes and determination of treatment. Including tonifying Qi, warmth and heat Yang, activating blood circulation to dissipate blood stasis,eliminating phlegm, to alleviate water retention and so on.Accompany with development of the science and technology, the modern medicine has great development in CHF pathogenesis. The change of the concept of CHF is the cell change, the heart compensation and the whole body neuroendocrine response from weakly pump and high resistance condition, realized the ventricle reconstruction is the basic mechanism of CHF after MI. The ventricle reconstruction causes the change of cardie cells' structure, function and phenotype, the activation of neuroendocrine. These factors caused and affect each other, become a vicious circle. Therefore, the key point is how to prompt cardiac cell to regenerate, decrease its apoptosis, prevent the ventricle reconstruction and decrease the rate of death.The stem cell technological development was rapidly in recent years. Studies in using cell transplant to regenerate cardiac muscle, reduces apoptosis, prevents the ventricle reconstruction and improve heart function becomes a hot spot. In the current research, usage of the marrow stem cell transplantation technology includes: Opens the chest direct injection;the intervention technology of catheter and the bone marrow stem cell mobilization (namely "self- transplant", "home position transplants" technology). The massive animal experimentation and the clinical research verified: the marrow mesenchyma stem cell (MSC) may differentiate into the cardiac cell by artificial induction in vitro. After transplanted to area of infarctus, it can emerge effective electricity -mechanical coupling with the periphery host cardiac cell. In the aspect of induction in vivo, using the stem cell mobilization medicine is able to cause the marrow stem cell to release into the circumference blood, and homing to the area of lack blood voluntarily. Under the microenvironment, it will differentiate into the functional cardiac cell.At present, there are no study on mobilize marrow stem cell to treat CHF after MI or inducing MSC into cardiac muscle cell by using Chinese herb in domestic and foreign, but there are many research prompts applying effective herb in treat stroke successfully inducing MSC into neuron cell. Selects effective herbs certificated by clinical and experimental study such as ginseng, aconite, astragali, ilexpubesceus and herba leonuri, changes them into blood serum contain medicine, and free, cultivate, appreciate and amplification MSC in vitro, then induce its differentiation. Appreciation, bolting these herb whether or not have the contribution in induce MSC differentiate into cardiac cell, as well as study its contribution in marrow stem cell mobilization. This will provide rationale and experiment evidence for Chinese herb combine with cellular transplant in treat cardiovascular disease such as CHF.Second part clinical researchThe mobi I ize function to bone marrow stem eel I by Yiqi Wenyang Huoxuefang and its influence on heart function to myocardial infarct patient1 ObjectiveObserve the mobilize function to stem cell by Yiqi Wenyang Huoxuefang (YQWYHXF) and its influence to heart function of myocardial infarction patient.2 Method2.1 Grouping and treatment:60 examples of acute myocardial infarction patient is divided into observed group and contrasted group randomly, each group contains 30 examples. Use conventional medicine treatment, Chinese herb (Gualou Xiebai Banxiatang) is gave everyone. Observed group is gave YQWYHXF (ginseng lOg, astragali 30g, monkshood 5g, ilexpubesceus 15g, herb leonuris 15g) additional, once a day and last 10 days.2.2 Detect index:2.2.1 At the instant of hospitalization, the 3rd, 7rd, 14rd, 20rd descript conventional 12 leads electrocardiogram, score the QRS value, and forecast the infarct size.2.2.2 Detect the quantity of CD+34 cell in blood at the 3rd and the lOrd days.2.2.3 At the first day hospitalization and the 3rd weekend, by use of the echocardiogram to detect the left ventricular end-diastolic volume (LVEDV), the left ventricular end-systolic volume (LVESV) and the left ventricular ejection fraction (LVEF). At the same time, observe the wall motion and calculate the ventricular movement score index.3 Result3.1 Compared with contrasted group, the quantity of CD+34 cells in blood of observe group are higher than contrasted group at treated 5 days and 10 days, there is significance difference (PO.01).3.2 Compare 21 days with the first day, the QRS score and infarct size of observation group remarkable drop (P<0.01);QRS score and infarct size of observation group at 21st day significant decrease than 21 days contrasted group (P<0.01), there is remarkable difference.3.3 Compared with contrasted group, the LVEDVI, LVESVI and the left ventricular wall movement of observation group at 21st day observation are remarkable reduction (all is P<0.01), its LVEF remarkably elevates (P<0.01), there are significance difference4 Conclusion4.1 YQWYHXF has a good effect in mobilize bone marrow stem cell.4.2 By mobilize stem cell, YQWYHXF can decrease the infarct size, containment thereconstruction of left ventricle, improve heart function, and has a better therapeutic efficacy than contrasted group.Third part experimental studyExperement 1 The influence to left ventricle reconstruction of heart to model rat with myocardial infarction by mobiIize bone marrow stem eel I with Yiqi Wenyang Huoxuefang.1 Objective1. Contrast and observe the bone marrow stem mobilization induced by YQWYHXF and G-CSF.2. Contrast and observe the influence of YQWYHXF and G-CSF to left ventricle reconstruction to MI model rat.2 Methods2.1 Groupings and treatment: The SD rats is divided into blank group, model group, medicine group and Chinese herb group randomly, each group contains lO.merely rats. Start therapy the second day after make model. Blank group: injected with 0.2ml physiological saline in subcutaneouly, filled the stomach with 5ml physiological saline;Medicine group: filled the stomach with 5ml physiological saline, injected with lOug/kg d rhG-CSF in subcutaneouly;Chinese herb group: filled the stomach with 5ml Chinese herb, injected with 0.2ml physiological saline in subcutaneouly. All treatment is once a day and last 10 days.2.2 Detecting the quantity of CD+34 cell in blood with flow cytometery after treated 5 days and 10 days.2.3 Observing the left ventricle reconstruction:After be treated 8 weeks, weighting the rat, takes out the heart and weight it, calculate the heart index;Manufacting left ventricle pathological section, examines the left ventricle area (LVA), the left ventricle cavity area (LVCA).Calculating the expansion index(EI) and the thinning ratio(TR).3 Results3.1 5 days after be made model, the number of bone marrow stem in blood increase 10 times in medicine group and the Chinese herb group, there are extremely remarkable difference compared with the model group (PO.001);After withdrawal medicine 5 days, the number of bone marrow stem cell in Chinese herb group has decreased, but still maintained in comparable higher level, compared with medicine group, the difference is remarkable (PO.001).3.2 Compared with model group, the heart weight and the weight index in CSF group and the Chinese herb group are remarkable drop (P<0.001);compared with the blank group, their heart weight and the weight index elevates, has the significance difference (PO.05). Compared with CSF group the heart weight and the weight index decreased, but there are no statistics difference between CSF group and Chinese herb group.3.3 Compared with model group, the LVA and the LVCA of model group and Chinese herb group remarkable drop (respectively is P<0.05, PO.001). There are no statistics difference between CSF group and Chinese herb group.3.4 Compared with models group, the TR of CSF group and Chinese herb group elevates (PO.05), the El of CSF group and Chinese herb group decreased (PO.001). Compared with CSF group, the TR elevates and the El decreased in Chinese herb group, but there is no statistics difference between them.4 Conclusions4.1 YQWYHXF has a good mobilization effect to bone marrow stem cell, and the mobilizing effectiveness of Chinese herb is better than CSF.4.2 Through mobilize the bone marrow stem cell, YQWYHXF drop the heart weight and the weight index, decrease area of left ventricle cavity and the left ventricle wall, reduce the expansion index, the thinning ratio increase. All this demonstrate that mobilization of the stem cell by YQWYHXF can inhibiting the left ventricle reconstruction of heart, improving the function of heart and decreasing the area of myocardial infarction. It is better than CSF.Experement 2 Blood serum contain Chinese herbs induce marrow mesenchyma stem cell differentiate into the cardiac cell1 ObjectiveTo observe the contribution of blood serum contain Chinese herbs induce marrow mesenchyma stem cell differentiate into the cardiac muscle cell and select the effective herbs.2 Method2.1 preparations blood serum contains herbs:Japanese big ear white rabbit 12 merely, divided into the blank group, the ginseng group, the aconite root group, astragali group, ilexpubesceis group and the herba leonuri group randomly, each group contain 2 merely. Filled the stomach with 9ml/d.kg the corresp Chinese herb;10 days later, picks the blood from carotis. Separating blood serum aseptically, deactivating and storing for use later.2.2 inductions and differentiations:Clean level SD rats are used, aseptically decoherence its shinbone, femoral bone, take its marrow liquid solution. Separate the marrow mesenchyma stem cells (MSC) by gradient separate accompany with difference adherence to the wall, conventional culture and passage it. The 8th generation of MSC is divided into blank group, 5-Azacitidine group, bland blood serum group and Chinese herb group. Blank group does not use any antileptic, 5- Azacitidine group uses lxlO^mmol/L 5-Azacitidine induces for 24 hours;bland blood serum group apply blank blood serum to induce for 24 hours;The Chinese herb groups apply blood serum contains ginseng, aconite root, astragali, ilexpubesceus and herba leonuri respectively, according to the induce time (24h, 48h, 72h), divide it into three subgroup again. After be inducted, convention cultivanted.2.3 Detect surface antigen of MSC with Flows cytometry;Detect protin expression of troponin and desmin after inducted.3 Results3.1 Flow cytometry detection indicate: CD34 is negative, CD44 is positive, the positive rate above 98%. Demonstrate that its homogenicity is good after 8 generation.3.2 blanks group, blank blood serum, ginseng, ilexpubesceus, monkshood and herba leonuri groups have no expression in troponin and desmin protein. But it is discovered in 5-Azacitidine and astragali groups. The positive rate of troponin cells is 20% and 13%, the Desimin dells is 32% and 29%.3.3 blanks group and ginseng, ilexpubesceus, monkshood and herba leonuri groups have no positive strap of a-MHC and P-MHC. But it is discovered in 5-Azacitidine and astragali groups. Demonstrate MSC express the specific myoglobulin gamma chain of cardiac muscle cell after been inducted.4 ConclusionsBlood serum contain astragali can induce MSC differentiate into cardiac type cell.