尼可地尔、谷氨酰胺、美托洛尔单独及联合使用抗大鼠心肌缺血/再灌注损伤的保护作用

The protective effects of nicorandil,glutamine and metoprolol used in single and combination against myocardial ischemia/reperfusion injury in rats

目的:研究尼可地尔(nicorandil,Nic)、谷氨酰胺(glutamine,Glu)、美托洛尔(metoprolol,Met)三药联用对大鼠在体心肌缺血再灌注(ischemia reperfusion,IR)损伤的保护作用。方法:将健康Wistar雄性大鼠随机分为7组:(1)假手术(sham)组,只开胸,行冠状动脉左前降支(left anterior descending,LAD)穿线;(2)缺血再灌注损伤(IR)组,行心脏LAD30 min缺血/120 min再灌注程序;(3)尼可地尔(Nic)组;(4)谷氨酰胺(Glu)组;(5)美托洛尔(Met)组;(6)尼可地尔、谷氨酰胺、美托洛尔联合用药(NGM)组;(7)尼可地尔、谷氨酰胺、美托洛尔联合用药低剂量(NGML)组。药物预处理组则在IR程序前30 min腹腔注射相应药物,Nic、Glu、Met的初始给药剂量为1 mg·kg-1(1 mg·ml-1),1 mg·kg-1(1 mg·ml-1),1 mg·kg-1(1 mg·ml-1)。监测各组心肌IR损伤期间的心脏生理学情况;损伤后心肌梗死面积和形态学改变;于120 min再灌注末取血测定肌酸激酶MB同工酶(creatine kinase-MB,CK-MB)、髓过氧化物酶(myeloperoxidase,MPO)、超氧化物歧化酶(superoxide dismutase,SOD)活性和丙二醛(malonaldehyde,MDA)含量。结果:对于大鼠在体心肌IR损伤,Nic、Glu、Met联合用药组与药物单用组相比能明显增强心脏生理功能;降低IR损伤所致心肌梗死面积,改善损伤的心肌细胞形态学改变;减少CK-MB的漏出和MPO分泌,增加心肌细胞抗氧化能力,提高SOD活性,减少MDA含量。结论:Nic、Glu、Met联合用药可以对大鼠在体心肌IR损伤起到保护作用。

OBJECTIVE To investigate the protective effects and mechanism of nicorandil （Nic）, glutamine （Glu） and meto- prolol （Met） used in single or combination against myocardial ischemia reperfusion （IR） injury in vivo in rats. lVlETItODS Male Wistar rats were divided randomly into seven groups： （1） sham operated group： didn＇t ligate the coronary artery; （2） IR group： only 30 min ischemia and 120 min reperfusion of LAD was conducted; （3） Nic group; （4） Glu group; （5） Met group; （6） Nic ＋ Glu ＋ Met （NGM） group; （7） low dose of Nic ＋ Glu ＋ Met （NGML） group. In the pharmacological precondition groups, the corresponding drugs were administrated ahead 30 min of IR protocol, and the initial drug doses were 1 mg. kg-~ （1 mg. ml- 1 ）, 1 mg. kg^-1 （1 mg. ml^-1）, 1 mg. kg^-1 （1 mg. ml ^-1 ）. Heart physiology of each group during the period of IR was monitored. Assessed the myocardial infarct size and morphology after IR. At the end of the reperfusion, the activity of creatine kinase-MB （CK-MB）.myeloperoxidase （MPO）,superoxide dismutase （SOD） and malonaldehyde （MDA） in the plasma of rats were measured. RESULTS Compared with single therapy after IR in rat, the combination therapy of Nic, Glu and Met could do better in the following aspects： strengthening heart physiological function obviously; shrinking IS and improving morpholog ical changes caused by IR~ redu reducing CK-MB leakage and MPO secretion; increasing the antioxidation ability of cardiocytes through elevating SOD activity and reducing MDA content. CONCLUSION The combination therapy of Nic, Glu and Met can protect against IR.