Angiotensin 1-7 attenuates left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy
10.3760/cma.j.issn.0253-3758.2012.03.009
- VernacularTitle:血管紧张素(1-7)对阿霉素扩张型心肌病大鼠心功能和心肌细胞凋亡的影响及其机制
- Author:
Hong-Zhi LIU
1
;
Chuan-Yu GAO
;
Xian-Qing WANG
;
Hai-Xia FU
;
Hong-Hui YANG
;
Xian-Pei WANG
;
Yu-Hao LIU
;
Mu-Wei LI
;
Zhen-Min NIU
;
Guo-You DAI
;
Da-Tun QI
;
You ZHANG
Author Information
1. 河南省人民医院
- Keywords:
Cardiomyopathies;
Epirubicin;
Angiotensins;
Apoptosis
- From:
Chinese Journal of Cardiology
2012;40(3):219-224
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect Angiontensin(1-7) [Ang(1-7)] on left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopthy ( ADR-DCM ).Methods Weight-matched adult male Wistar rats were randomly divided into 3 groups:( 1 )the ADR-DCM group (n =25 ),in which 2.5 mg/kg of ADR was weekly intravenously injected for 10 weeks.( 2 ) Ang ( 1-7 ) group ( n =25 ),in which ADR rats were simultaneously treated with angiotensin-(1-7) (24 μg · kg-1 · h-1,ip.) for 12 weeks.(3) normal control group (n =10).Hemodynamics and echocardiography examination were performed at 12 weeks.The malondialdehyde (MDA) was measured by TBA methods.The plasma concentration of Ang Ⅱ was determined by immunoradiometric assay.The pathological change was analyzed by histological hematoxylin-eosin staining.Myocardial apoptosis was assessed by TUNEL method.The protein expression of pro-apoptotic protein caspase-3,Bax and antiapoptotic protein Bcl-xl in cardiomyocytes were detected by Western blot.Results Mortality was significantly lower in Ang(1-7) group than in ADR-DCM group (16％ vs.40％,P ＜0.01 ).Compared to the control group,left ventricular end-diastolic diameter ( LVEDD),left ventricular end systolic diameter (LVESD) and left ventricular end-diastolic pressure (LVEDP) were significantly increased in ADR-DCM group ( all P ＜ 0.01 ) while fractional shorting ( FS), + dp/dtmax and - dp/dtmax were significantly reduced in ADR-DCM group ( all P ＜0.01 ).LVEDD,LVESD and LVEDP were significantly reduced while FS,+ dp/dtmax and -dp/dtmax were significantly higher in Ang( 1-7 ) group compared to the ADR-DCM group,but still higher than the control group ( all P ＜ 0.01 ).The concentrations of Ang Ⅱ and MDA were higher in the ADR-DCM group than in the control group ( P ＜ 0.01 ),which were significantly reduced by Ang(1-7) treatment (P ＜ 0.01 ).The TUNEL-positive cells and apoptosis index,the expression of proapoptotic protein caspase-3 and Bax were significantly higher while the expression of anti-apoptotic protein Bcl-xl was significantly lower in the ADR-DCM group than in the control group (all P ＜ 0.01 ) which could all be partially reversed by Ang(1-7) treatment ( all P ＜ 0.01 ).Conclusion Ang (1-7) could significantly attenuate left ventricular dysfunction and myocardial apoptosis in this model by downregulating pro-apoptotic protein caspase-3 and Bax and upregulating anti-apoptotic protein Bcl-xl expression.
