摘要
目的观察美托洛尔与特布他林联用对心梗大鼠心功能的影响，从心肌细胞凋亡及氧化应激角度探讨其机制。方法结扎冠状动脉前降支制备心梗大鼠模型，随机分为美托洛尔组（M组）、特布他林组（T组）、联合治疗组（L组）和安慰剂组（A组），另选一组为假手术组（S组），每组8只。术后1周灌胃给药，M组给予美托洛尔20mg／kg，T组给予特布他林2mg／kg，L组给予美托洛尔和特布他林，剂量同上，A组给予等量生理盐水，S组不予处理。生理盐水及药物皆为2次／d灌胃。8周后行超声心动图、血流动力学、心肌组织GSH／GSSG、bax／bcl-2蛋白测定。结果①用药组LVEDD、LVESD较A组明显降低（P〈0．05），EF、FS明显升高（P〈0．05），T组与L组较M组进一步改善（P〈0．05）。②用药组LVEDP较A组明显降低（P〈0．05），LVSP、＋dp／dt明显升高（P〈0．05），L组较M组进一步改善（P〈0．05），T组LVEDP较M组明显降低（P〈0．05）。③用药组谷光甘肽（GSH）较A组明显升高（P〈0．01），氧化型谷光甘肽（GSSG）明显降低（P〈0．01），L组较单药治疗组进一步改善（P〈0．05），T组与M组相比，GSH明显升高（P〈0．05）。④用药组bcl-2较A组明显升高（P〈0．01），bax明显降低（P〈0．01），T组与L组bax水平接近（P=0．141），两组较M组明显降低（P〈0．05），L组bcl-2水平与S组接近（P=0．453），两单药治疗组bcl-2差异无统计学意义（P=0．132），均显著低于L组，L组bcl-2／bax明显高于T组，T组bcl-2／bax明显高于M组。结论特布他林对心梗后大鼠心功能及心室重构的改善作用优于美托洛尔，二者联用改善作用进一步增强。其相关机制可能与改善心肌组织氧化应激、明显减轻心肌细胞凋亡有关。
Objective To observe the effect of combined therapy of metoprolol and terbutalin in rat model of post-myocardial infarction, and to explore the mechanism of apoptosis and oxidative stress of myocardial cells. Methods We established the rat model of post-myocardial infarction by ligating the left descending coronary artery. The AMI rats were randomly divided into five groups： （1）Treated with metoprolol. （2）Treated with terbutalin. （3）Treated with the combination of metoprolol and terbutalin. （4）Treated with normal saline. （5）Sham group. There are 8 rats in each group. Treatment was started one week after surgery. The daily dose was 20 mg/kg, 2 mg/kg for metoprolol and terbutalin respectively（twice daily/gavage）. LV dimensions,the content of GSH/GSSG, the expressionlevels of bax/bc1-2 protein, UCG, hemodynamic index were evaluated after 8 weeks＇ treatment. Results （1） LYEDD, LVESD, LVEDP, GSSG, bax protein, were significantly lower in treatment groups while EF, FS, LVSP, ＋ dp/dt, GSH, bel-2 protein, bcl-2/bax significantly higher than those in placebo group. These changes were more significant in combined treatment group （all P〈0.05 vs metoprolol group）. （2）LVEDP, bax protein was reduced, GSH, bcl-2/bax increased in terbutalin group （all P〈0.05 vs metoprolol group）. （3）Compared with combined treat- ment group, bcl-2 protein, bcl-2/bax was reduced in any monotherapy alone, and bcl-2 protein in these groups did not show statistical significance（P=0.132 ）. In the terbutalin group, the LV function parameters were significant- ly improved （compared to metoprolol ） and this improvement was similar to that of combined treatment group. Conclusion Combined therapy of metoprolol and terbutalin was superior in the improvement of LV function and ventricular remodeling over any monotherapy alone. This superiority might contribute to the effects of reducing my- ocardium apoptosis and improving oxidative stress.
出处
《中国心血管病研究》
CAS
2013年第6期463-467,共5页
Chinese Journal of Cardiovascular Research
关键词
美托洛尔
特布他林
心室重构
氧化应激
细胞凋亡
Metoprolol
Terbutalin
Ventricular-remodeling
Oxidative-stress
Apoptosis
