2023 年第 12 期 第 18 卷

左西孟旦联合浅低温对大鼠心肌缺血再灌注损伤的协同保护作用研究

Investigating the synergistic protective effect of levosimendan combined with shallow hypothermia on myocardial ischemia-reperfusion injury in rats

作者：李露露蒙延海李泽蒙张燕搏

英文作者：Li Lulu Meng Yanhai Li Zemeng Zhang Yanbo

单位：中国医学科学院北京协和医学院国家心血管病中心阜外医院成人外科恢复室，北京100037

英文单位：Surgery Intensive Care Unit Fuwai Hospital National Cardiovascular Center Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100037 China

关键词：心肌缺血再灌注损伤；左西孟旦；浅低温；协同保护

英文关键词：Myocardialischemia-reperfusioninjury;Levosimendan;Shallowhypothermia;Synergisticprotection

• 摘要：

• 目的  探讨左西孟旦联合浅低温治疗对大鼠心肌缺血再灌注损伤（MIRI）的协同保护作用。方法  将20只SD大鼠随机分为左西孟旦联合浅低温治疗组（LM组）、左西孟旦治疗组（L组）、浅低温治疗组（M组）、对照组（C组），每组5只，结扎大鼠左冠状动脉前降支，制作大鼠MIRI模型。不同组别大鼠给予相应剂量(12 μg/kg)的左西孟旦或0.9%氯化钠溶液，在再灌注的同时以［0.3 μg/（kg·min）］静脉输注2 h，并进行浅低温（33.0±0.5）℃或常温（37.0±0.5）℃干预维持2 h，观察并记录血流动力学指标。再灌注结束后检测心肌损伤标志物乳酸脱氢酶（LDH）和肌酸激酶同工酶（CK-MB），之后进行2,3,5-氯化三苯基四氮唑染色观察心肌梗死程度。结果  再灌注2 h后，LM组、L组、M组平均动脉压及收缩压均高于C组［（87±8）、（76±7）、（74±4）mmHg（1 mmHg=0.133 kPa）比（63±7）mmHg；（121±9）、（101±10）、（100±10）mmHg比（86±5）mmHg］，且LM组平均动脉压及收缩压均高于L组及M组，差异均有统计学意义（均P＜0.05）。再灌注2 h后，LM组、L组、M组LDH及CK-MB水平均低于C组［（1 290±194）、（1 590±205）、（1 718±174）U/L比（2 135±209）U/L；（1 060±35）、（1 356±214）、（1 631±201）U/L比（2 029±261）U/L］，且LM组LDH及CK-MB水平均低于L组和M组，差异均有统计学意义（均P＜0.05）。LM组、L组、M组心肌梗死体积比均低于C组［（25±5）%、（38±4）%、（41±5）%比（63±9）%］，且LM组心肌梗死体积比均低于L组和M组，差异均有统计学意义（均P＜0.05）。结论  左西孟旦联合浅低温治疗可减轻大鼠的MIRI，通过改善血流动力学、减轻心肌损伤及心肌梗死程度达到协同保护作用。

• Objective To investigate the synergistic protective effect of levosimendan combined with shallow hypothermia on myocardial ischemia-reperfusion injury in rats. Methods Totally 20 SD rats were randomly divided into levosimendan combined with mild hypothermia treatment (LM) group, levosimendan treatment (L) group, mild hypothermia treatment (M) group and control (C) group, 5 rats per group. The anterior descending branch of the left coronary artery of rats was ligated to make a model of myocardial ischemia-reperfusion injury. Rats in different groups were given the corresponding dose (12 μg/kg) of levosimendan or 0.9% sodium chloride injection, which was infused intravenously at 0.3 μg/(kg·min) for 2 h while reperfusion, and maintained at shallow hypothermia (33.0±0.5)℃ or normothermia (37.0±0.5)℃ intervention for 2 h. Hemodynamic indexes were observed and recorded. Myocardial injury markers lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) were detected at the end of reperfusion, followed by 2,3,5-triphenyltetrazolium chloride staining to observe the volume of myocardial infarction. Results  After 2 h of reperfusion, the mean arterial pressure and systolic blood pressure in the LM group, L group and M group were higher than those in the C group［(87±8), (76±7), (74±4)mmHg vs (63±7)mmHg；(121±9), (101±10), (100±10)mmHg vs (86±5)mmHg］, and the levels in LM group were higher than those in the L group and M group (all P＜0.05). After 2 h of reperfusion, the levels of LDH and CK-MB in LM group, L group and M group were lower than those in C group［(1 290±194), (1 590±205), (1 718±174)U/L vs (2 135±209)U/L；(1 060±35), (1 356±214), (1 631±201)U/L vs (2 029±261)U/L］, and the levels of LDH and CK-MB in LM group were lower than those in L group and M group (all P＜0.05). The myocardial infarction volume ratio in LM group, L group, and M group was lower than that in C group ［(25±5)%, (38±4)%, (41±5)% vs (63±9)%］, and the myocardial infarction volume ratio in LM group was lower than that in L group and M group(all P＜0.05). Conclusion Levosimendan combined with mild hypothermia treatment attenuated myocardial ischemia-reperfusion injury in rats and achieved synergistic protective effect by improving hemodynamics and reducing myocardial injury and myocardial infarct size.