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Effects Of Granulocyte Colony-stimulating Factor On The Myocardial Infarction In Experimental Rabbits

Posted on:2005-08-23Degree:MasterType:Thesis
Country:ChinaCandidate:S L XiaFull Text:PDF
GTID:2144360122472250Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Sudden occlusion of a major coronary artery and acute myocardial ischemia lead to rapid death of myocytes. The loss of myocytes in the infarcted area is irreversible, resulting with time in the formation of scarred tissue. Recently new therapeutic methods such as percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass grafting(CABG) are able to reperfuse the occuled coronary artery, but not regenerate the myocytes. Although heart transplantation is an option for patients in severe congestive heart failure post acute MI, organ shortage and the need for immunosuppression detract from whole organ transplantation. In 1990s some study showed that transplanted smooth muscle cells, skeletal myoblast cells, cardiomyocytes and embryonic stem cells should limited scar expansion and prevent development of heart failure, but these cells were eventually eliminated by rejection. Recently some research showed after transplantated into the myocardial infarction region, the bone marrow-derived mesenchymal cells could transdifferente into cardiomyotes and ameliorate the function of the injuried heart. This approach, howeve required a surgical intervention that was accompanied by high mortality and a low grafting success rate. Therefore, the utilization of a nonvasive method would be highly desirable. Wehypothesized that a sufficient number of bone marrow cell mobilized by granulocyte colony-stimulating factor (G-CSF) would home to the infarcted heart and promote cardiac repair. To test this possibility, New Zealand rabbits with ligation of coronary artery were injected with G-CSF to increase the number of circulating stem cells.Materials and MethodsNew Zealand rabbits were randomly divided into sham-operation (SO) group, myocardial infarction(MI) group and G-CSF treatment(GT) group. Myocardial infarction was induced by ligation of coronary artery. The rabbits of GT group were treated with G-CSF 10ug/kg subcutaneously before 24h of ligation of coronary artery and for 6 days after surgery once a day. Those of SO group and MI group were received saline. Brdu 18.5mg/kg body weight, was given once a day for 14 day before the rabbits in each group were killed. Ecocardiography was performed in each group before surgery and after 4 weeks. The hearts were harvested at 4 weeks for HE, anti-Brdu and anti-Troponin I immunohistochemistry pathological examination.Results1. The number of white blood cells, neutrophills in peripheral circulation increase 2-7, 2-10 times respectively, after the rabbits of GT group were treated with G-CSF 10ug/kg subcutaneously for 7 days.2. The mortality of GT group(20%,2/10) was lower than that of MI group (40%, 4/10) and higher than SO group (0% ,0/10) after 4 weeks (P<0.05).3. EF of GT group(0.705+ 0.038) were higher than MI group(0.554+0.065 ) (P<0.05) and low than SO group (0.757+0.019) after 4 weeks.4. In the current study, the number of capillaries of GT group in the infarcted areas was larger than that of MI group. Some capilliary walls were composed of Brdu-positive endothelial cells. No myocytes were seen in each group.Conclusion1. Bone marrow cells mobilization by G-CSF result in a dramtic increase in survival of rabbits.They can migrate into peripheral circulation and proliferate, differentiate.2. G-CSF treatment could be benefical to the regeneration of vascular structures and improve cardiac function.
Keywords/Search Tags:Granulpcyte Colony-stimulating Factor, Myocardial Infarction, Rabbits
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