| Objective:(1) To analyze the effect of Wenyangzhenshuai on the activation of renin-angiotensin-aldosterone system (RAAS) in animal experimental models of chronic heart disease, and to investigate the therapy mechanism of Wenyangzhenshuai to chronic heart disease.(2) To analyze the effect of Wenyangzhenshuai on the ventricular remodeling in animal experimental models of chronic heart disease, and to investigate the mechanism of Wenyangzhenshuai to myocardial structure of chronic heart disease.And this reaesrch would provide the objective laboratory evidence to treatment of chronic heart disease by traditional chinese medicine.Methods:The68healthy male New Zealand rabbits (clean grade) were purchased from Vital River experimental animal center of Beijing. All New Zealand rabbits were randomly divided into6groups.①normal control group,11male New Zealand rabbits were randomly drawn and were fed with isometric distilled water by intragastric administration. And the residua57male New Zealand rabbits were received adriamycin by intravenous injection to establishment of experimental animal model of chronic heart failure. After animal model establishment, all male New Zealand rabbits were received echocardiography. The57male New Zealand rabbits which were compliance with requirements of chronic heart disease were chosen to research. Based on the left ventricle ejection fraction (LVEF) from the echocardiography, the57male New Zealand rabbits were graded and divided into5groups randomly, which were②animal model group, male New Zealand rabbits were fed with isometric distilled water by intragastric administration; ③high-dosage group, male New Zealand rabbits were fed with high-dosage wenyangzhenshuai,10g/(kg·d);④medium-dosage group, male New Zealand rabbits were fed with medium-dosage Wenyangzhenshuai,5g/(kg·d);⑤low-dosage group, male New Zealand rabbits were fed with low-dosage Wenyangzhenshuai,2.5g/(kg·d);⑥furosemide group, male New Zealand rabbits were fed with furosemide,2.0mg/(kg·d). Continuous application to all male New Zealand rabbits were4weeks qd.(1) The analysis of normal baseline indexes. The differences of normal baseline indexes were compared among six groups, including mental status, respiration, heart rate, activity, reaction, body weight, diet, stool, urine, fur, etc.(2) The analysis of all indexes of RAAS. The blood sample was get from the New Zealand rabbits’ear vein. And the plasma indexes of plasma renin activity (PRA), angiotensin Ⅱ AngⅡ), aldosterone (ALD) and Beta ntriuretic peptide (BNP) were detected by ELISA. The plasma indexes of plasma renin activity (PRA), angiotensin Ⅱ (Ang Ⅱ), aldosterone (ALD)and Beta ntriuretic pptide (BNP) at pre-and post-experiment were compared among6groups.(3) The analysis of function indexes of ventricular remodeling. The ventricular function indexes of left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic dimension (LVEDD), left ventricular posterior wall (LVPW), left ventricle ejection fraction (LVEF), left ventricular fractional shortening (LVFS), ventricular septal thickness (IVS), early diastolic peak velocity of mitral flow (E), atrial systolic peak velocity of mitral flow (A) and E/A at pre-and post-experiment were detected by echocardiography and compared among6groups.(4) The analysis of gross tissue indexes of ventricular remodeling. After experiment, the male New Zealand rabbits were anaesthesia and were taken heart by thoracotomy. The wet weigh of the left and right ventricle, including interventricular septum, were weigh accurately. And the ratios of left ventricle weight (LVW) and the body weight (BW) were calculated, then the left ventricle weight index (LVWI) and the body weight index (BWI) were also calculated.(5) The analysis of pathomorphism indexes of ventricular remodeling. The variations of pathomorphism under light microscope and electron microscope were observed and compared among six groups.Results:(1) The comparison of normal baseline indexes. All normal baseline indexes, including mental status, respiration, heart rate, activity, reaction, body weight, diet, stool, urine, fur, etc. were no different among six groups before study (all P>0.05). The all normal baseline indexes of normal control group after animal model establishment and drug administration were no different than before study (all P>0.05). The sequence of other five groups on the improvment degree of normal baseline indexes was high-dosage group> medium-dosage group> low-dosage group> furosemide group> animal model group (all P<0.05).(2) The analysis of all indexes of RAAS. The plasma levels of plasma renin activity (PRA), angiotensin Ⅱ AngⅡ), aldosterone (ALD) and Beta ntriuretic pptide (BNP) in animal model were no different among six groups before study (all P>0.05). The all RAAS indexes of normal control group after animal model establishment and drug administration were no different than before study (all P>0.05). The sequence of other five groups on the plasma levels of RAAS indexes was high-dosage group<medium-dosage group<low-dosage group<furosemide group<animal model group (all P<0.05).(3) The analysis of function indexes of ventricular remodeling. The plasma levels of ventricular function indexes of left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic dimension (LVEDD), left ventricular posterior wall (LVPW), left ventricle ejection fraction (LVEF), left ventricular fractional shortening (LVFS), ventricular septal thickness (IVS), early diastolic peak velocity of mitral flow (E), atrial systolic peak velocity of mitral flow (A) and E/A in animal model were no different among six groups before study (all P>0.05). The all ventricular remodeling function indexes of normal control group after animal model establishment and drug administration were no different than before study (all P>0.05). The sequence of other five groups on the levels of LVEF and LVFS was high-dosage group> medium-dosage group> low-dosage group>furosemide group>animal model group (all P<0.05). The sequences of other five groups on the levels of LVESD, LVEDD, LVPW, IVS and E/A were high-dosage group<medium-dosage group<low-dosage group<furosemide group<animal model group (all P<0.05).(4) The analysis of gross tissue indexes of ventricular remodeling. The gross tissue indexes of the left ventricle weight index (LV WI) and the body weight index (BWI) in animal model were no different among six groups before study (all P>0.05). The all gross tissue indexes of normal control group after animal model establishment and drug administration were no different than before study (all P>0.05). The sequences of other five groups on the left ventricle weight index (LVWI) and the body weight index (BWI) were high-dosage group<medium-dosage group<low-dosage group<furosemide group<animal model group (all P<0.05).(5) The analysis of pathomorphism indexes of ventricular remodeling. The damage variations were observed by pathomorphism in the other five groups of animal model establishment. The sequences of other five groups on the pathological changes were high-dosage group<medium-dosage group<low-dosage group<furosemide group<animal model group.Conclusion:(1) Wenyangzhenshuai can improve efficiently the proceeding of ventricular remodeling in animal model of chronic heart disease.(2) Wenyangzhenshuai can suppress prominently the activation of RAAS in animal model of chronic heart disease.(3) Wenyangzhenshuai can regulate the ventricular remodeling and RAAS in animal model of chronic heart disease. And this effect was dose dependent. Larger dose of Wenyangzhenshuai, the better of effect. |
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