Effects of pretreatment with metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization in rats
10.3760/cma.j.issn.0253-3758.2013.08.014
- VernacularTitle:美托洛尔预处理对大鼠冠状动脉微栓塞后心肌细胞凋亡及天冬氨酸特异性半胱氨酸蛋白酶-8活化的影响及意义
- Author:
Qiang SU
1
;
Lang LI
;
You ZHOU
;
Jiang-You WANG
;
Wei-Ming WEN
;
Yong-Guang LU
Author Information
1. 广西医科大学第一附属医院心内科广西心血管病研究所
- Keywords:
Coronary vessels;
Embolism;
Metoprolol;
Apoptosis
- From:
Chinese Journal of Cardiology
2013;41(8):693-697
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization (CME) in rats.Methods Adult rats were randomly assigned into CME group (intraventricular injection of 3000 microspheres with 42 μm in diameter),shamoperated group (0.1 ml saline) and CME plus metoprolol group (pretreatment with 3 bolus metoprolol 2.5 mg/kg intravenous injection at 10 minutes interval at 30 minutes before microspheres injection,n =15,each group).Cardiac function was evaluated by echocardiography at 6 hours post various treatments.Cardiomyocyte apoptosis was detected with TUNEL staining and the expression of caspase-3 and caspase-8 was detected with Western blot analysis.Results Compared with sham-operated group,LVEF (72.68％ ±3.26％ vs.82.64％ ±3.43％,P ＜0.05),fractional shortening (FS) (37.46％ ±2.38％ vs.42.85％ ±3.25％) and cardiac output (CO) [(0.101 ±0.006) L/min vs.(0.162 ±0.008) L/min] were significantly reduced while left ventricular end-diastolic diameter(LVEDd) [(6.22 ± 0.17) mm vs.(5.18 ±0.43) mm] was significantly increased in CME group (all P ＜ 0.05).Cardiac function [LVEF:73.94％ ±4.22％,FS:38.53％ ±2.03％,CO:(0.120 ±0.012) L/min,LVEDd:(6.18 ±0.27) mm] was similar in CME plus metoprolol group compared to CME group (all P ＞ 0.05).The cardiomyocytes apoptosis rates (3.19％ ± 1.23％ vs.0.18％ ±0.10％) and the levels of activated caspase-3 and caspase-8 proteins were significantly increased in CME group than in sham-operated group (all P ＜ 0.05).The cardiomyocyte apoptosis rate (1.32％ ± 0.28％) and the levels of activated caspase-3 and caspase-8 proteins were significantly lower in CME plus metoprolol group than in CME group (all P ＜0.05).Conclusions Metoprolol pretreatment reduced post-CME myocardial apoptosis possibly through downregulating death receptor-mediated apoptotic pathway.
