| BackgroundThe morbidity of coronary heart disease in our country is increasing and it remains the leading cause of mortality in industrialized countries. Besides traditional drug treatments, interventional therapy and surgical intervention of coronary artery bypass graft etc. have been adopted extensively and developed greatly. But their application is limited with the shortcomings of trauma, relative adaptation and restenosis. In the beginning of 70's, Folkman and his colleagues studied the growth of blood vessels and the substances involved in it in tumor. In the following thirty years, scholars have made profound studies on the growth of blood vessels under various kinds of pathologic and normal conditions, with basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) being considered as the critical growth factor during angiogenesis. It can be observed that the concentration and expression of bFGF and VEGF increase in the patient's ischemic myocardium and its border, but there are no significant perennial newly-born vessels to improve blood supply in clinical progress. Adenosine is considered to be the angiogenic factor that relates the changes of metabolism to the compensatory angiogenesis. There were more and more reports on the function of adenosine on angiogenesis during the past ten years. From the beginning of 90's with the successive studies on its effect on angiogenesis and growth factor in models in tumor, retinopathy, hypertension, myocardiol infarction, myocardial hypertrophy, the angiotensin system is considered to have effect on angiogenesis. Angiotensin converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor antagonist(ATlRA) have good effect on ventricular remodeling, amelioration of hemodynamics and reduction of congestive heart failure. But there are fewer studies of theireffect on angiogenesis and growth factor involved in it.ObjectiveThough studies show that the concentration and expression of bFGF and VEGF increase in the ischemic myocardium and its border in coronary heart disease, there is no significant increase of perennial newly born vessels to improve the blood supply in clinical progress. Additionally, the effect of ACEI and AT1RA on angiogenesis is still not clear. In our experiment, we established the acute myocardial infarction model of rabbit and studied the effect of intervention of bFGF, adenosine, ACEI and AT1RA on angiogenesis of the heart, trying to track down the reason for the inhibited angiogenesis of ischemic myocardial and the lack of formation of collateral, and thus find basis for clinical therapy.MethodWe established acute anterior myocardial infarction model by ligating anterior descending branch of coronary artery of the Japan-sino hybridization white rabbit. After operation the rabbits were divided into nine groups randomly and each group is treated with different drugs. Group 1: administered saline(NS), 8ml iv qd*28 days; group 2: administered NS, 8ml iv qdx!4days; group 3: administered bFGF, lOug/kg iv qd*28days; group 4: administered bFGF, lOug/kg iv qd><14days; group 5: administered adenosine, 3mg/kg ivCcontinue 5~10min)qdxl4days; group 6: administered bFGF, lOug/kg iv qdx!4day and adenosine, 3mg/kg iv (continue 5~10min) qd><14days; group 7: administered benazepril (lotensin) lOmg/kg/d ip*14days; group 8: administered benazepril lOmg/kg/d ip*14days and bFGF lOug/kg iv qdxHdays; group 9: administered valsartan(Diovan) 40mg/kg/d ip*14days. The rabbits were killed on the 14th day or 28th day and the hearts were removed and fixed in formaldehyde, and then were cut into 2mm slices from apex to base and embedded with paraffin. The basal side of each equatorial slice were sliced up and the sections were handled with HE (hematoxylin and eosin) stain and Masson trichrome stain, and the immunohistochemical study of VEGF, bFGF and CD34. We carried out observations on the pathologic changes in the zone of infarction, the border zone of infarction and the zone far from infarction, selected 5~10 visual fields r... |
PDF Full Text Request