| Background: Ventricular remodeling are defined as the changes process of the ventricular size and structure and cardiac function. This process including the bulge in myocardial infarcted area, cardiac myohypertrophia in uninfarcted area, thicked ventricular wall, myocardium interstinal fibrosis, ventricular dilation and cardiac dysfunction.It is the main reason that cause myocardial infrction patients died. Bone marrow stem cell can improve cardiac function, but the mechanism are unclear now. Bone marrow stem cell transplant can inhibiting myocardial remodeling, prevent cadiocyte hypertrophy and matrix reconstitution, decreasing myocardial fibrosis, promoting vascular remodeling and angiogenesis and decrease cadiocyte apoptosis. Autologous bone marrow mononuclear cells mesenchymal stem cells and progenitor cells are the main kinds for cardiac cellular transplant.Objective: To study the influnce of transplanting autologous bone marrow mononuclear cells and mesenchymal stem cells in acute myocardial infarction models on ventricular remodeling, and to investigate the mechanism of transplating different kind of stem cells on acute myocardial infarction models. To simulate the procedure of percutaneous transluminal coronary angioplasty on patients and to evaluate the safety and effect of transplanting stem cells.Method: Thirty-six male white swines was randomly divided into control group, acute myocardial infarction pattern, bone marrow mononuclear cells and mesenchymal stem cells group.By meaens of over the wire balloon we transplant stem cells into infarcted area.1. The swine models of acute mycardial infarction were established by means of puncturing femoral artery or carotid artery by obstructing left anterior descending artery.2. Bone marrow mononuclear cells were separated by means of density gradient centrifugation and symboled by gold colloid. mesenchymal stem cells were cultured by adherence method.3. Self bone marrow mononuclear cells and mesenchymal stem cells were transplanted into the left anterior descending artery after ninety minute of acute myocardial infarction.4. Echocardiography were taken at preoperative and postoperative immediately and twenty eight day after cellular transplant respectively.5. The number of blood capillary, myocardial nuclear factor-кB expression, myocardial apoptosis and myocardial proliferating cell nuclear antigen expression were detected by means of light and electron microscope and immunohistochemistry .6. Myocardial vascular endothelial growth factor and basic fibroblast growth factor were detected by way of real time quantity reverse transcription polymerase chain reaction twenty-eight day after acute myocardial infarction.Result:1. The establishment of cardia failure swine models after acute myocardial infarction. Twenty-eight days later, the thirty-one survival swines among the thirty-six acute myocardial infarction models were as follows, six swines survial in sham group and eight swines survial in both myocardial infarction and mesenchymal stem cells groups and nine swines in bone marrow mononuclear cells group. After left anterior descending occlusion two hours,the amplitude of ST elevated was 0.43士0.35mv. The creatine kinase level were 112.50±70.23;1190.50±734.05;1162.55±837.23;1142.00±308.90 in sham group; myocardial infarction group; bone marrow mononuclear cells group and mesenchymal stem cells groups respectively(F=4.80,P=0.008). The MB isoenzyme of creatine kinase level were 15.33±5.85;121.62±74.11;101.77±79.65;105.25±42.42 in sham group; myocardial infarction group; bone marrow mononuclear cells group and mesenchymal stem cells groups respectively(F=3.93,P=0.019). The cTnI level were 2.48±1.13;49.66±44.73;55.05±47.42;45.61±26.73 in sham groups; myocardial infarction groups; bone marrow mononuclear cells groups and mesenchymal stem cells groups respectively(F=2.78,P= 0.06). The creatine kinase, MB isoenzyme of creatine kinase and cTnI level in myocardial infarction groups; bone marrow mononuclear cells groups and mesenchymal stem cells groups were significantly higher than that in sham groups.But the levels were no significant deviation among stem cells transplant groups and myocardial infarction groups.The levels of end-systolic dimension, end-diastolic dimension, ejection fraction, fractional shortening had no significant deviation preopration. Two hours after myocardial infarction the ejection fraction in myocardial infarction groups; bone marrow mononuclear cells groups and mesenchymal stem cells groups were significantly lower than those in sham groups(646.2%士23.62%;45.13%士33.02%;47.2%5士5.41% vs 1.70%士3.91% ,F=23.88 P=0.0001).There were no ignificant deviation among stem cell transplant groups and myocardial infarction groups.In myocardial infarction groups, by light microscope, a large number of myocadial fibration were found in the infarcted zone. In stem cell groups, a great number of inflammatory cells were found in the infarcted and marginal zone. In stem cell groups, by electron microscope, a great number of fibroblast were found in infarction zone.2. Bone marrow mononuclear cell and mesenchymal stem cells separation and cultivation and inductive differentiation. After density gradient centrifugation, we can found the white bone marrow mononuclear cell layer between separating medium and blood plasma. The mesenchymal stem cells growth adherence within seventy-two hours, two days later it began to proliferate quickly and the colony augmentate gradually. Within nine and eleven days, the clony mixed togher and the cells showed fusiform shape at the mean time nucelus get into comparatively large and the chromatospherite disintegrate. When eighty to nighty percent colony had been mixed toghter, we taken digestion and passage. Every culture bottle we can get 5.5×105 esenchymal stem cells. Seven days later, these cells began to confluens and amplification.After ten days these cells the velocity of increase began to slow down.3. The effects of intracoronary autologous bone marrow mononuclear cells and mesenchymal stem cells on ventricular remodeling after acute myocadial infarction.At the end of twenty-eight days the swine's end-diastolic diameter in sham and stem cell groups were obviously smaller(F=5.30,P=0.005) and the ejection fraction and fractional shortening were higher(F=10.67,P=0.0001;F=6.64,P=0.0017)than those in myocardial infarction groups. The wall motion abnormalities index in bone marrow mononuclear cells and mesenchymal stem cells groups were more decreased than those in infarction groups (2.44±0.72 and 2.25±0.46 vs 3.25±1.03 F=11.95,P=0.001), the index were no significant difference between stem cells groups.At the end of twenty-eight days, there were a great quantity of vascular proliferation, abnormal cells growth and blood capillary gemmation in infarction and marginal zone in bone marrow mononuclear cells groups. There were some colloid positive immature cadiocyte growth in the marginal zone in mesenchymal stem cells groups.In infarction model groups and bone marrow mononuclear cells and mesenchymal stem cells groups, the numbers of blood vessels were significantly increased than those in sham groups. In bone marrow mononuclear cells groups the number of blood vessels were significantly increased than those in mesenchymal stem cells groups(infarction zone F=34.87 P=0.0001,marginal zone F=29.56 P=0.0001).In marginal zone, in infarction groups, bone marrow mononuclear cells and mesenchymal stem cells groups the nuclear factor-кB expression were increased than those in sham groups(F=19.05,P=0.001). In stem cells groups the nuclear factor-кB expression were more decreased than those in infarction groups. In infarction and marginal zone, in infarction groups, bone marrow mononuclear cells and mesenchymal stem cells groups the cadiocyte apoptosis were more increased than those in sham groups(infarction zone F=14.31,P=0.0001 marginal zone F=35.34,P=0.0001). There were no significant differences between stem cell groups.In bone marrow mononuclear cells and mesenchymal stem cells groups the myocardial troponin I and nuclear proliferate antigen-кB expression were more increased than those in myocardial infarction groups.In infarction and marginal zone, in infarction model groups and bone marrow mononuclear cells and mesenchymal stem cells groups, the expression of vessel endothelium growth factor were more increased than those in sham group(sinfarction zone F=20.11 P=0.0001; marginal zone F=49.41 P=0.0001). The marginal zone, in bone marrow mononuclear cells groups, the vessel endothelium growth factor were more increased than those in mesenchymal stem cells groups. In bone marrow mononuclear cells groups and mesenchymal stem cells groups the basic fibroblast growth factor expression were higher than those in myocardial infarction groups(F=23.69,P=0.0001),and there were no significant difference between stem cell groups.The ejection fraction had a negative correlation with cadiocyte apoptosis(r=-0.4411,P=0.0273) and nuclear proliferate antigen-кB(r=-0.5796,P=0.0006); had a postive correlation with the numbers of blood vessels(r=0.775 , P=0.0003)and the expression of vessel endothelium growth factor(r=0.5651,P=0.0181) and basic fibroblast growth factor(r=0.5857, P=0.0171). The myocardial apoptosis had a postive correlation with the nuclear proliferate antigen-кB.Conclusion:1. We set up the equality myocardium necrosis swine models of post-myocardial infarction by means of balloon occlusive method.2. We obtained the bone marrow mononuclear cells and mesenchymal stem cells by use of gdensity gradient centrifugation and adherence method, at the mean time we use gold colloid as labelling lmarker to reduce the marker's toxic action.3. Both bone marrow mononuclear cells and mesenchymal stem cells transplantation can retard left ventricular remodeling, myocardium apoptosis, nuclear proliferate antigen-кB expression and increase the expression of vessel endothelium growth factor and basic fibroblast growth factor and add the number of myocardial blood vessels.The transplanted cells can alive in the myocardial infarction marginal zone.4. The cardiac function had a negative correlation with myocardium apoptosis and nuclear proliferate antigen-кB expression and positive correlation with he numbers of blood vessels and the expression of vessel endothelium growth factor and basic fibroblast growth factor.5. The effect of promoting cardiac vascular proliferation of transplant bone marrow mononuclear cells was surpassed to that of transplant mesenchymal stem cells. The expression of basic fibroblast growth factor in marginal zone by tranplant mesenchymal stem cells was surpassed to that of transplant bone marrow mononuclear cells.After transplant of mesenchymal stem cells, the transplant cells in marginal zone was more alive than that by transplanting bone marrow mononuclear cells.
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