| Objective: With the acceleration of the industrialization process and the improvement of people’s living standards, ischemic heart disease, especially myocardial infarction has become a major killer. When myocardial infarction happens, alarge amount of myocardial cells undergo necrosis and apoptosis. For a long time heart was considered a postmitotic organ and has limited regenerative capacity,once damaged, cannot go through their own mitosis and repair. Fibroblasts andits secretion of collagen material cannot form functioning tissue to replace the original heart tissue. This lack of regenerative ability seriously affects the normal cardiac systolic and diastolic function. The gradual deterioration in cardiac function ultimately leads to heart failure and death. Current treatments focus on interventional therapy and heart transplantation, which are not only expensive but alsolimited by graft immune rejection and short supply of donor organs. The critical thing is that the cardiocytes number cannot be restored to solve the problem of ventricular remodeling. Recent research shows that, the heart contains a pool ofprimitive cells—cardiac stem cells（CSCs）, which have potential cardiac differentiation ability. CSCs can differentiate like pluripotent stem cells. At present, a group of cells which has the strongest proliferation capacity and is studied widelyis the c-kit-positive CSCs, which, on its surface, expresses stem cell factor receptor c-kit. CSCs’ differentiation and proliferation are closely related to the microenvironment. By a variety of biologically active substances’ induction, such as cytokines or growth factor, CSCs can differentiate into cardiac structural cells likecardiocytes, endothelial cells, smooth muscle cells etc. BMP-2and FGF-2in themicroenvironment have affects on CSCs’ migration and differentiation. But the induction and differentiation mechanism of CSCs by the two factors is not clear, and therefore, still need further research. CSCs’ study and development has undoubtedly opened up a new way for the clinical treatment of myocardial infarctionand at the same time brought hope to the patients with myocardial infarction. This study is aimed at detecting BMP-2, FGF-2and c-kit’s expression and correlation in human cardiac tissues by immunohistochemical S-P method, and to compare their expression difference in patients with myocardial infarction and normalpersons, and then discuss the effect of BMP-2and FGF-2on the differentiationof c-kit+CSCs during the process of developing myocardial infarction and after the infarct has occurred. This can supply a new idea for the clinical treatment ofmyocardial infarction using stem cells transplantation.Methods: A total of60cases, autopsy archived paraffin blocks were taken from the Department of Pathology and Forensic medicine, Dalian Medical University. Twenty (20) cases were selected for normal myocardium group,40cases were myocardial infarction group and all the cases were confirmed by histological examination. The death time was within one week after myocardial infarction, and all thecases were autopsied within48hours after death. For each specimen, pieces of tissue had been taken from the left ventricular anterior wall, lateral wall, and posterior wall, interventricular septal and apical, paraffin-embedded serial sections, using the immunohistochemical S-P method for the detection of the expression of BMP-2, FGF-2and c-kit in normal myocardium、 myocardium infarction area and the area surrounding the infarction.The results were statistically analyzed in order to know their correlation, then further understand the factors that affect the mobilization and differentiation of CSCs.Results:1.BMP-2was weakly expressed in normal myocardium, strongly positive expression in myocardial infarction and the infarction surrounding area, mainly expressed in the cytoplasm or membrane of myocardial cells. The differences in the BMP-2expression in normal myocardium, myocardial infarction, and infarction surrounding areas were statistically significant (P <0.05).2. FGF-2was weakly expressed in1/4normal myocardium, strong positive expression in myocardial infarction.The positive expression in infracted myocardium (85%,80%) was significantly higher than that of normal myocardium (25%). FGF-2was mainly expressed in the cytoplasm of myocardial cells, endothelial cells and inflammatory cells (neutrophils and monocytes). FGF-2expression in the normal myocardium, myocardial infarction, and infarction surrounding area had a significant difference (P<0.05).3.c-kit was express ed in a small amount in normal myocardium and the majority samples did not have any expression. However, it was strongly expressed in the myocardial infarction group, mainly in the infarct area and infarct surrounding area. It was observed that round or long spindle cells were with brown or claybank cytoplasm in clumps concentration distribution among myocardial cells. C-kit expression in normal myocardium, myocardial infarction and infarction surrounding area had significant differences (P <0.05).4.Spearman rank correlation test showed that expression of BMP-2,FGF-2and c-kit in the myocardial infarction group has a significant correlation.Conclusion:1.There was a small amount of c-kit+CSCs in the normal heart,when myocardial infarction occurred, the number of such cells increases.2. BMP-2and FGF-2were expressed slightly in normal myocardial tissue, but highly expressed in the infracted myocardium and infracted surrounding area andtheir expressions in myocardial infarction were positively correlated, suggesting that the two have a synergistic effect in improving microenvironment after myocardial infarction.3. BMP-2and FGF-2were involved in c-kit+CSCs’ mobilization and differentiation. |
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