CAJ | 학술논문

目的：探讨左旋卡尼汀（LCN）预处理对体外循环下心肌缺血-再灌注损伤的保护作用及其机制。方法择期行体外循环下心脏瓣膜置换术患者60例，性别不限，年龄25～57岁，美国麻醉师（ASA）分级Ⅱ或Ⅲ级，美国纽约心脏病学会（NYHA）分级Ⅱ或Ⅲ级，随机平均分为2组：C 组（生理盐水作对照）和 L 组（左旋卡尼汀预处理）。 L 组于术前7 d 起，静脉滴注 LCN 50 mg/kg ，每天1次，直至手术当日；C 组给予等容量生理盐水。于麻醉诱导后5 min（T0，基础状态）、主动脉阻断前5 min （T1）、主动脉开放后30 min （T2）、术后6 h （T3）、12 h （T4）和24 h （T5）取颈内静脉血测定心肌肌钙蛋白 I（cTnI）、肌酸激酶同工酶（CK-MB）和肿瘤坏死因子α（TNF-α）水平；于主动脉阻断前和开放后，取右心房部分心肌组织，观察心肌细胞病理结构，并用蛋白免疫印迹法（Western blot）检测心肌 p38丝裂原活化蛋白激酶（p38MAPK）及其磷酸化蛋白的表达；于术前1 d 和术后7 d 行心脏彩超测定患者心脏指数（CI）和左室射血分数（LVEF）。结果与 C 组比较，L 组主动脉开放后各时点 cTnI 、CK-MB 和 TNF-α水平降低（P＜0．05），心肌细胞线粒体损伤较轻，p38MAPK 及其磷酸化蛋白的表达减弱（P＜0．05）。术后第7天 L 组 CI 和 LVEF 均高于C 组（P＜0．05）。结论 LCN 预处理可减轻体外循环心肌缺血-再灌注损伤，利于心功能的恢复，其机制可能与保持线粒体膜和空间结构的完整性，下调心 p38MAPK 及其磷酸化蛋白的表达，并抑制炎症反应有关。
목적：탐토좌선잡니정（LCN）예처리대체외순배하심기결혈-재관주손상적보호작용급기궤제。방법택기행체외순배하심장판막치환술환자60례，성별불한，년령25～57세，미국마취사（ASA）분급Ⅱ혹Ⅲ급，미국뉴약심장병학회（NYHA）분급Ⅱ혹Ⅲ급，수궤평균분위2조：C 조（생리염수작대조）화 L 조（좌선잡니정예처리）。 L 조우술전7 d 기，정맥적주 LCN 50 mg/kg ，매천1차，직지수술당일；C 조급여등용량생리염수。우마취유도후5 min（T0，기출상태）、주동맥조단전5 min （T1）、주동맥개방후30 min （T2）、술후6 h （T3）、12 h （T4）화24 h （T5）취경내정맥혈측정심기기개단백 I（cTnI）、기산격매동공매（CK-MB）화종류배사인자α（TNF-α）수평；우주동맥조단전화개방후，취우심방부분심기조직，관찰심기세포병리결구，병용단백면역인적법（Western blot）검측심기 p38사렬원활화단백격매（p38MAPK）급기린산화단백적표체；우술전1 d 화술후7 d 행심장채초측정환자심장지수（CI）화좌실사혈분수（LVEF）。결과여 C 조비교，L 조주동맥개방후각시점 cTnI 、CK-MB 화 TNF-α수평강저（P＜0．05），심기세포선립체손상교경，p38MAPK 급기린산화단백적표체감약（P＜0．05）。술후제7천 L 조 CI 화 LVEF 균고우C 조（P＜0．05）。결론 LCN 예처리가감경체외순배심기결혈-재관주손상，리우심공능적회복，기궤제가능여보지선립체막화공간결구적완정성，하조심 p38MAPK 급기린산화단백적표체，병억제염증반응유관。
Objective To evaluate the protective effects and mechanism of levocarnitine preconditioning (LCN) on myocardial is-chemia-reperfusion injury in patients undergoing cardiopulmonary bypass .Methods 60 cases of ASA Ⅱ or Ⅲ degree and NYHAⅡ or Ⅲ degree patients who aged 25 ~ 57 years old ,undergoing cardiopulmonary bypass with elective cardiac valve replacement were randomly divided into 2 groups (n = 30 each) :group C (treated with 0 .9% sodium chloride) and group L (treated with LCN) .Group L was infused levocarnitine 50 mg/kg per 1 day at the beginning of 7 days before operation ,group C was given the same amount of 0 .9% sodium chloride .Blood samples were taken from central vein at 5 min after the induction the level of anesthe-sia (T0 ,baseline) ,5 min before aortic cross-clamping (T1) ,30 min after release of the aortic cross-clamp (T2) and at 6 (T3) ,12 (T4) and 24 h (T5) after operation for determination .The level of plasma cardiac troponin I (cTnI) ,creatine kinase-MB (CK-MB) and tumor necrosis factor-α (TNF-α) .Myocardial specimens were obtained from right auricle before aortic cross-clamping and after release of aortic cross-clamp to observe the pathologic changes ,the protein expression of p38 MAPK and phosphorylational-p38 MAPK that analyzed by western blotting .Cardiac index (CI) and left ventricular ejection fraction (LVEF) were measured at 1st day before operation and 7th day after operation by using heart color ultrasonography .Results The levels of cTnI ,CK-MB and TNF-α were significantly lower at all time points in group L than in group C (P< 0 .05) .Myocardial mitochondrion impairment was lighter ,the expression of p38 MAPK and phosphorylational-p38 MAPK were significantly attenuated in group L than in group C (P< 0 .05) .CI and LVEF were significantly higher at 7th day after operation in group L than in group C(P< 0 .05) .Conclusion Le-vocarnitine preconditioning can attenuate myocardial ischemia-reperfusion injury and recover cardiac function in patients undergoing cardiopulmonary bypass ,the mechanism may be related to keep the integrity of the mitochondrial membrane and space structures , inhibit the expression of p38 MAPK and phosphorylational-p38 MAPK and decrease the inflammatory response .