| Objective to investigate the effects of varying doses of simvastatin for chronic heart faile (CHF) rabit of Protein Kinase A (PKA)、(Soluble Leukocyte cell differentiation antigens40, SCD40L) ventricular remodeling and heart function, to provide a new direction, and of simvastatin in patient with chronic heart failure occurred in the development of possible mechanisms for the curing heart faile.Methods Sixty male rabbits, weighed2.0-2.5kg, provided by the Experimental Animals’ Center of Xinxiang Medical University, were randomly divided into five groups (12rabbits in each group):control group (CON), CHF group, small-dose simvastatin group (SD-SIM), medium-dose simvastatin group (MD-SIM), and the high-dose simvastatin (HD-SIM). Except for the control group, the other4groups received adriamycin (1.5mg/kg) injection diluted by normal saline (1mg/ml), once a week for10weeks through the auricular vein of rabbits, which were observed2weeks after injection. The control group were injected the same doses of normal saline with the other groups, and the same way of administration and the duration of drug use. The SD-SIM, MD-SIM and (HD-SIM groups were injected varying dosages of simvastatin together with adriamycin for the first time,0.3mg.kg-1.d-1for The SD-SIM,1.5mg.kg-1.d-1for MD-SIM. and3mg.kg-1.d-1for HD-SIM, diluted separately with5ml saline by intragastric administration for12weeks. The CHF and the CON groups received the same volume of saline by intragastric administration for12weeks. Two weeks after adriamycin injection, Color Doppler ultrasonography were taken to detect for the ventricular left structure and the function, and the hemodynamic indexes, Before the rabbits were sacrificed by the carotid artery to take blood5mL preset anticoagulant tube,4℃,5000r/min,centrifuged30min after centrifugation serum was stored at-70℃refrigerator, with enzyme marker immune assay (Elisa) monitoring of soluble CD14expression levels of40(Soluble Leukocyte cell differentiation antigens40SCD40L), while specimens from the heart, ventricular wall set paraformaldehyde, HE staining of myocardial cell changes in the structure immunohistochemical staining to detect protein kinase A (the Protein kinase A) expression.and then the rabbits were sacrificed. Then some of ventricular walls were taken for fixation with formaldehyde.By HE staining of myocardial cell structure changes, immunohistochemical staining to detect protein kinase A (the Protein kinase A) and enzyme-labeled immunosorbent assay (Elisa) monitoring of soluble leukocyte differentiation antigen40(Soluble Leukocyte cell differentiation antigens40SCD40L) expression levels.ReusultS Compared with the control group, the specimens showed that the left ventricle became attenuated and ventricular chambers got expanded,the SD-SIM group and the HD-SIM group, while some CHF rabbits partly showed hydropericardium, Bloody ascites, hydrothorax, but there was no significant changes in MD-SIM group.The heart function examinations also demonstrated that the left ventricular blood ejection fraction (LVEF)all droped sharply in this group compared with CON group (P<0.01). compred with the SD-SIM and the HD-SIM groups, the Left ventricular end diatolic diameter (LVDd) and Left ventricular end systolic diameter (LVSd) of the MD-SIM group were drouped markedly (P<0.05).Hemodynamic exams indicated that the Pressure maximal rate of rise (+dp/dtmax)、the Pressure maximal rate of fall (-dp/dtmax) and Left ventricular systolic pressure (LVSP) in the CHF group dropped significantly compared with CON group (P<0.01), the CHF group compared to the MD-SIM group resed significantly (P <0.05).HE staining displayed that in the CON group the number of the myocardial cells had decreased, lamellar necrosis. In the simvastatin therapy groups, the overall situation wasbetter than the CHF group, but the myocardial cells also had varied dimensions; in the myocardial cells of the SD-SIM and the HD-SIM groups, the microstructural proliferations were found; the myocardial cells of MD-SIM group were better arranged compared with CON group. PKA expression in the myocardiumthe:PKA in the SD-SIM, the MD-SIM, HD-SIM expression increased significantly (P<0.05), compared to the expression of which HD-SIM group and SD-SIM, MD-SIM, more(P<0.05) of CHF group and other groups. sCD40L expression in the myocardiumthe:Compared with the CON group, the SD-SIM, the MD-SIM, HD-SIM, sCD40Lsignificantly (P<0.05), compared to the CHF and the HD-SIM group, the MD-SIM group was significantly incresed (P<0.05).Conclusion PKA expression and activity in heart failure is to reduce, sCD40L expression is elevated, PKA and sCD40L are involved in the occurrence of CHF, the development and severity of heart failure. Simvastatin can significantly improve the delay chronic heart failure rabbit left ventricular remodeling and improve cardiac function. |
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