摘要
目的观察不同剂量卡维地洛对高压负荷性心衰幼鼠心室重构的防治作用。方法采用腹主动脉缩窄术建立慢性心力衰竭(CHF)模型,36只存活雄性5周龄Wistar幼鼠随机分组:(1)CHF对照组(n=8);(2)大剂量卡维地洛组(10mg·kg-1·d-1,n=10);(3)中剂量卡维地洛组(1mg·kg-1·d-1,n=10);(4)小剂量卡维地洛(0.1mg·kg-1·d-1,n=8);另设假手术对照组。直接灌胃给药,给药4周后行高频超声、血流动力学、心脏病理分析、心肌细胞凋亡及其检测血清中脂质过氧化物(LPO)和超氧化物歧化酶(SOD)含量。结果与假手术组比较,CHF组左室收缩末期内径(LVESD)、室间隔舒张末期厚度(IVSTd)、室间隔收缩末期厚度(IVSTs)、左室后壁舒张末期厚(LVPWTd)、左室后壁收缩末期厚度(LVPWTs)左、右心室相对重量(LVRW,RVRW)、收缩压(SBP)、舒张压(DBP)、左室收缩压(LVSP)、左室舒张末压(LVEDP)、凋亡指数(AI)、LPO均显著升高(P<0.01),左室舒张末期内径LVEDD也明显升高(P<0.05)。左室短轴缩短率FS、左室射血分数EF、左室内压最大收缩率(+dp/dtmax)、左室内压最大舒张率(-dp/dtmax)、SOD均显著降低(P<0.01)。与CHF组比较,卡维地洛组LVEDD、LVESD、IVSTd、IVSTs、LVPWTd、LVPWTs、LVRW、RVRW、SBP、DBP、LVSP、LVEDP、AI、LPO均呈剂量相关性下降,以大中剂量下降明显(P<0.05或P<0.01),FS、EF、+dp/dtmax、-dp/dtmax、SOD均显著升高(P<0.01)。结论卡维地洛大、中、小剂量均能有效防治幼鼠CHF发展中的心室重构,改善血流动力学和心功能,阻止心肌细胞凋亡和清除氧自由基;小剂量有效,大剂量更佳。
Objective To study the effect of carvedilol on ventricular remodeling in chronic heart failure（CHF） resulting from pressure overload in juvenile rats. Methods The CHF animal model of rats was established by constriction of abdominal aorta Thirty-six surviving male rats of five weeks old were randomly divided into CHF control group（n=8）, large dose carvedilol （10 mg· kg^-1 ·d^-1 ,n= 10） group, middle dose carvedilol （1 mg · kg^-1 · d^-1 , n= 10） group, and small dose carvedilol（0.1 mg ·kg^-1· d^-1 ,n=8 group）. Sham operated rats （n=8） were selected randomly as non-infarction control. Carvedilol was administered by direct gastric gavage After 4 weeks of drug therapy, the high frequency ultrasonography（HFUS）, hemodynamic analysis, pathologic analysis of the hearts and cardiac myocyte apoptosis analysis were performed. The serum contents of lipid pereoxidation（LPO） and superoxide dismutase（SOD） were detected. Results Compared with the sham operated group, LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW, RVRW, SBP, DBP, LVSP,LVEDP, AI, LPO were all significantly increased（P〈0.01） in CHF group, so did LVEDD （P〈0.05）. A significant decrease could be seen in EF, FS, ＋dp/dtmax,- dp/dtmax, SOD. In comparison with CHF group, a dose-dependent and significant decrease could be seen in LVEDD, LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW, RVRW, SBP, DBP, LVSP, AI, LPO and LVEDP,especially in the large and middle dose carvedilol groups（P〈0.05 or P〈0.01）. While a significant increase could be seen in EF, FS, ＋ dp/dtmax, - dp/dtmax, SOD （P〈0.01）. Conclusion Carvedilol in no matter what dose effectively and dose-dependently prevents ventricular remodeling in CHF juvenile rats.
出处
《江苏医药》
CAS
CSCD
北大核心
2008年第2期166-169,219,共5页
Jiangsu Medical Journal
关键词
卡维地洛
心室重构
心肌细胞凋亡
氧化应激
Carvedilol
Ventricular remodeling
Myocardial apoptosis
Oxidation stress
