伊伐布雷定对病毒性心肌炎小鼠的心功能和儿茶酚胺作用

Effects of ivabradine on left ventricular function and plasma norepinephrine in a murine model of the coxsackie virus B3-induced viral myocarditis

目的:探讨伊伐布雷定和卡维地洛对急性病毒性心肌炎小鼠心功能以及循环儿茶酚胺的作用。方法:随机将150只雄性BALB/C小鼠分为4组:空白对照组(n=30),心肌炎组(n=40),伊伐布雷定组(n=40),卡维地洛组(n=40)。后3组经腹腔接种CVB3诱发急性病毒性心肌炎,空白组腹腔注射磷酸缓冲液,接种当天记为第0天,24 h后伊伐布雷定组和卡维地洛组每日灌胃分别给予伊伐布雷定10 mg/kg、卡维地洛10 mg/kg,空白组给予磷酸盐缓冲液灌胃,直至第14天末。分别于接种第4天、7天、14天随机从各组抽取小鼠测心率血压,行心脏B超检查,计算心脏重量与体重的比值(HW/BW),HE染色观察炎症病理改变,采用高效液相色谱-电化学法检测血浆去甲肾上腺素(NE)浓度改变。结果:与空白对照组比较,心肌炎组在第4天、7天、14天心肌病理损伤明显增加、HW/BW比值显著增加、血浆NE浓度明显增加,并且心超证实在第14天左室缩短分数、射血分数明显下降。与心肌炎组比较,第7和14天,伊伐布雷定组和卡维地洛组小鼠心率均明显降低,心肌病理损伤明显减轻、HW/BW比值明显下降。第14天,伊伐布雷定组和卡维地洛组均较心肌炎组左室射血分数、缩短分数明显增加。卡维地洛组在第4天、7天、14天相较心肌炎组明显降低血浆NE浓度,伊伐布雷定组在14天较心肌炎组降低血浆NE浓度。结论:伊伐布雷定具有和卡维地洛相似的减轻心肌炎小鼠的心肌炎症损害的作用,其显著降低病毒性心肌炎小鼠心率,改善病毒性心肌炎小鼠心功能,并显著降低循环儿茶酚胺的浓度。

AIM： To compare the effects of ivabradine and carvedilol on left ventricular function and plasma norepinephrine in acute viral myocarditis. METHODS： BALB / C mice were intraperitoneally inoculated with coxsackie virus B3（ CVB3）,starting 24 h after infection ivabradine and carvedilol were administered orally in a dose of 10 mg · kg- 1·24 h- 1for 14 consective days respectively. Virus infection group and normal group were used with the same dose of PBS. The mice were killed on days 4,7 or 14. Heart rate,blood pressure,myocardial histopathological changes,ratio of heart weight to body weight（ HW / BW） ratio,cardiac function,and plasma noradrenaline were determined. RESULTS：Both ivabradine and carvedilol significantly reduced heart rate and HW / BW ratio,and attenuated myocardial lesions. Compared with the myocarditis group,the left ventricular fractional shortening and ejection fraction on day 14 were increased in the ivabradine and carvedilol groups. In addition,ivabradine treatment as well as carvedilol treatment showed a significant decrease in the amount of plasma noradrenaline. CONCLUSION： Ivabradine significantly attenuated myocardial lesions and improved the impairment of left ventricular function and reduced noradrenaline levels in the murine model of viral myocarditis. These results show that ivabradine has a therapeutic benefit in murine myocarditis induced by CVB3. The protective effect of ivabradine against viral myocarditis is probably the result of its heart rate reduction effects and the reducion of plasma noradrenaline.