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[ ABSTRACT] AIM:To investigate the different dose of perindopril on cardiac function in the rabbits with ische-mic cardiac dysfunction .METHODS:Male rabbits weighing 2.5~3.0 kg ( n=30) were randomly divided into 3 groups (n=10):high dose perindopril group (HD group), low dose perindopril group (LD group) and cardiac dysfunction group (CD group).The Left anterior descending coronary artery of the rabbits was ligatured for model preparation .In HD group, the rabbits were treated with perindopril split normal saline solution (1 g/L)2 mL· kg-1 · d-1 .In LD group, the rabbits were treated with perindopril split normal saline solution (0.33 g/L)2 mL· kg -1 · d-1.In CD group, the rabbits were treated with normal saline solution 2 mL· kg-1 · d-1 .Four weeks after treatment , the cardiac function was measured via echocardiography , the mRNA expression of angiotensin-converting enzyme 2 ( ACE2 ) and angiotensin type 2 receptor (AT2R) was analyzed by real-time PCR, serum angiotensin (Ang)-(1-9) and Ang-(1-7) levels were detected by ELISA. RESULTS:Compared with CD group , the cardiac function of the 2 groups treated with perindopril was significantly im-proved (P<0.01), and more improvement in HD group was observed than LD group (P<0.05).The serum angiotensin ( Ang)-(1-9) and Ang-(1-7) level and the mRNA expression of ACE 2 and AT2R in the 2 groups treated with perindopril were significantly improved (P<0.01).Compared with LD group, the mRNA expression of ACE2 and AT2R and the ser-um levels of Ang-(1-9) in HD group were significant improved (P<0.05), while no difference of serum Ang-(1-7) level was observed.Correlation analysis revealed that the improvement of the cardiac function was associated with serum Ang -(1-9) level, mRNA expression of ACE2 and AT2R (P<0.01), but has no significant correlation with serum Ang-(1-7) lev-el.CONCLUSION:High dose of perindopril may improve more cardiac function in ischemic cardiac dysfunction model in rabbits.The mechanism may relate to increasing serum Ang-(1-7) level to activate AT2R.
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[ ABSTRACT] AIM:To investigate the effects of transplantation of bone marrow mesenchymal stem cells ( BMSCs) modified by bcl-2 gene on myocardial cell apoptosis, angiogenesis and cardiac function in the rabbit after acute myocardial in-farction ( MI) .METHODS:The rabbit BMSCs were isolated, cultured and purified in vitro.The BMSCs were transfected with adenovirus or adenovirus-Bcl-2.The rabbit model of MI was established by ligation of left anterior descending branch. The rabbits were injected with Ad-Bcl-2-BMSCs ( MI+Bcl-2-BMSCs group) , Ad-BMSCs ( MI+BMSCs group) and DMEM ( MI group) in infarction marginal zone 2 weeks after ligation.The cardiac function was evaluated by echocardiography.The apoptosis of myocardial cells was measured by TUNEL.The mRNA expression of VEGF was detected by real-time PCR.The expression of CD31 was examined by immunohistochemical staining, and new blood capillaries were counted at 4 weeks after BMSCs transplantation.The correlation of the above values with cardiac function was analyzed.RESULTS: The cardiac function was better, the apoptotic rate was lower, the mRNA expression of VEGF and the capillary density were higher in both MI+Bcl-2-BMSCs group and the MI+BMSCs group than those in MI group, and those in MI+Bcl-2-BMSCs group in-creased more obviously .The left ventricular ejection fraction ( LVEF) had a negative correlation with the myocardial cell ap-optosis rate.A positive correlation with the mRNA expression level of VEGF and the capillary density was also observed. CONCLUSION:The transplantation of BMSCs modified by bcl-2 gene significantly reduces the myocardial cell apoptosis, promotes angiogenesis, improves heart function of the rabbits with MI.
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BACKGROUND:Bone marrow stem cell transplantation can improve heart function and prevent ventricle remodeling.At present,the adult bone marrow stem cells used for transplantation primarily included bone marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs),and endothelial progenitor cells.The curative effects and precise mechanisms of transplantation of various bone marrow stem cells remain unknown.OBJECTIVE:To compare the effects of transplantation of autologous BM-MNCs and MSCs via the coronary artery on ventricle remodeling subsequent to acute myocardial infarction (AMI). DESIGN,TIME AND SETTING:Randomized controlled animal experiment performed at the Center for Clinical Research,Hebei Provincial People's Hospital,Electron Microscope Room,Hebei Medical University between March 2005 and December 2006.MATERIALS:Thirty-six male Jizhong pigs,were randomly divided into 4 groups:control group (n = 6),infarct model group (n = 10),BM-MNC group (n = 10),and MSC group (n = 10).METHODS:Porcine autologous BM-MNCs were isolated by gradient density centrifugation,and MSCs were obtained by adherence method.Prior to transplantation,both BM-MNCs and MSCs were colloidal gold labeled.Except the infract model group,pigs in the other 3 groups were developed into AMI models by oppressing the left anterior descending branch with balloon catheter.Ninety minutes after modeling,(6.0±1.3)×107 autologous BM-MNCs and (4.5±2.1)x 107 MSCs were respectively transplanted into pigs in the BM-MNC group and the MSC group via the coronary artery and cultured for 28 days.MAIN OUTCOME MEASURES:Observation of pathological changes of cardiac muscle tissue by light and electron microscope;Examination of cardiac function by ultrasonograph;Detection of the number of blood vessels and apoptotic myocardial cells,and expression of nuclear factor-κB (NF-κB) and troponin Ⅰ and its correlation to cardiac function by immunohistochemistry;Detection of mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cardiac tissue as well as its correlation to cardiac function by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS:In the MSC group,there was proliferation of a great deal of blood vessels as well as growth of abnormal cell masses around the coronary vessels,while the BM-MNC group exhibited the "budding" of many capillary vessels.Prior to transplantation,cardiac function indices were basically similar among each group (F = 1.550,P＞0.05).Twenty-eight days after transplantation,left ventricular ejection fraction was significantly lower in the control,BM-MNC,and MSC groups than in the infarct model group (F = 5.30,P＜0.05),while endocardial fractional shortening was significantly higher (F = 10.67,P＜0.01).Compared with the infarct model group,the number of blood vessels in the infarct zone and infarct border zone was increased in the BM-MNC group (F=29.56-34.87,P＜0.01) and had no apparent change in the MSC group.In the BM-MNC and MSC groups,apoptotic myocardial cells in the infarct zone and infarct border zone were significantly reduced (F=14.31-35.34,P＜0.01 ) and troponin I expression rate was significantly increased (F=19.05,P＜0.01 ),as compared with the infarct model group.In addition,NF-κB positive rate in the infarct border zone was significantly lower in the BM-MNC and MSC groups than in the infarct model group (F=19.05,P＜0.01).VEGF gene expression level in the infarct border zone was significandy higher in the BM-MNC group than in the infarct model group and MSC group (F = 49.41,P＜0.01).bFGF gene expression level in the infarct border zone was significantly higher in the MSC group than in the infarct model and BM-MNC groups (F=4.71,P＜0.01).LVEF was negatively correlated to myocardial cell apoptosis rate and NF-κB level (r=-0.441 1,P＜0.05;r=-0.579 6,P＜0.01 ).LVEF was positively correlated to number of blood vessels,VEGF and bFGF expression (r=0.775,P＜0.01;r=0.565 1,P＜0.05;r=0.573 5,P＜0.05).CONCLUSION:Transplantation of both autologous BM-MNC and MSC via coronary artery can improve the condition of left ventricular remodeling subsequent to myocardial infarction.The improvement of cardiac functions is related to the increase of blood vessels,VEGF and bFGF expression,the decrease of myocardial cell apoptosis and NF-κ B level in cardiac muscle tissues after stem cell transplantation.BM-MNC transplantation better promotes blood vessel proliferation and VEGF expression in the cardiac tissue but produces worse effects on bFGF gene expression than MSC transplantation.
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Objective To investigate the influence of two different dose of atorvastatin on the prognosis and endothelial function in post-PCI acute coronary syndrom patients.Methods 92 post-PCI ACS patients were randomly divided into two groups,atorvastatin 20mg and atorvastatin 10 mg group.In each group the patients were treated with atorvasta- tin 20mg or 10mg respectively.After one month we add or decrease the dose of atorvastatin according to the blood lipid level.After 12 month the blood lipid level、FMD、NO、ET、NOS、UAP、AMI were compared between two groups. Results The clinical setting have no significant association between two groups before treating,After treated 1 and 12 month the TC,LDL-C level were significantly decreased as compared with the base level before treating in each group. After treated 1 month,in atorvastatin 20 mg group the TC,LDL-C level were significantly decreased and NO、NO/ET level were significantly higher than those in atorvastatin 10 mg group.During 12 month follow up the incidence of angina pectoris onset and rehospitalization were significantly higher in atorvastatin 10 mg group(P