摘要
目的探讨乌司他丁减轻体外循环(CPB)下心脏手术患儿围术期心肌损伤的机制与外周血单个核细胞(PBMCs)铁死亡的关系。方法择期行CPB下室间隔缺损修补术患儿60例,性别不限,年龄4~8岁,ASA分级Ⅱ或Ⅲ级,采用随机数字表法分为2组(n=30):对照组(C组)和乌司他丁组(UTI组)。采用静吸复合麻醉。UTI组将乌司他丁20000 U/kg用生理盐水稀释至100 ml,于切皮前20 min时经15 min中心静脉输注50 ml,于CPB 10 min时经15 min CPB管路滴注50 ml;C组以等容量生理盐水替代。于麻醉诱导后切皮前(T_(1))、CPB开始后30 min(T_(2))、CPB停止即刻(T_(3))及CPB停止后24 h(T_(4))时采集颈内静脉血样,采用ELISA法测定血浆氨基末端β型脑钠肽前体(NT-proBNP)、心肌肌钙蛋白I(cTnI)和肌酸激酶同工酶(CK-MB)的水平。采用改良的Ficoll密度梯度离心法提取PBMCs,采用比色法测定PBMCs Fe^(2+)、MDA浓度和SOD活性,Western blot法检测PBMCs长链脂酰辅酶A合成酶4(ACSL4)及谷胱甘肽过氧化物酶4(GPX4)表达水平。结果与T_(1)时比较,2组T_(2~4)时血浆NT-proBNP、cTnI和CK-MB水平升高,PBMCs Fe^(2+)、MDA浓度和PBMCs ACSL4表达水平升高,SOD活性和GPX4表达水平降低(P<0.05)。与C组比较,UTI组T_(2~4)时血浆NT-proBNP、cTnI和CK-MB水平降低,PBMCs Fe^(2+)、MDA浓度和ACSL4表达水平降低,SOD活性和GPX4表达水平升高(P<0.05)。结论乌司他丁减轻CPB下心脏手术患儿围术期心肌损伤的机制可能与抑制PBMCs铁死亡有关。
Objective To investigate the relationship between the mechanism of ulinastatin reducing perioperative myocardial injury and ferroptosis in peripheral blood mononuclear cells(PBMCs)in pediatric patients undergoing heart surgery under cardiopulmonary bypass(CPB).Methods A total of 60 pediatric patients of either sex,aged 4-8 yr,of American Association of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective repair of ventricular septal defect under CPB,were divided into 2 groups by a random number table method:control group(C group)and ulinastatin group(UTI group),with 30 cases in each group.Combined intravenous-inhalational anesthesia was used.In UTI group,ulinastatin 20000 U/kg was diluted to 100 ml in normal saline,50 ml was infused through the central vein over 15 min starting from 20 min before skin incision,and the remaining 50 ml was instilled through the CPB pipeline over 15 min starting from 10 min of CPB.The equal volume of normal saline was given instead in C group.Blood samples from the internal jugular vein were collected after anesthesia induction and before skin incision(T_(1)),at 30 min after start of CPB(T_(2)),immediately after termination of CPB(T_(3))and at 24 h after termination of CPB(T_(4))for determination of the levels of amino-terminal B-type pro-brain natriuretic peptide(NT-proBNP),cardiac troponin I(cTnI)and creatine kinase isoenzymes(CK-MB)in plasma by enzyme-linked immunosorbent assay.PBMCs were extracted by modified Ficoll density gradient centrifugation method for determination of the concentrations of Fe^(2+)and malondialdehyde(MDA)and activity of superoxide dismutase(SOD)in PBMCs(by colorimetric method)and expression of long-chain acyl-CoA synthase 4(ACSL4)and glutathione peroxidase 4(GPX4)in PBMCs(by Western blot).Results Compared with the baseline at T_(1),the levels of NT-proBNP,cTnI and CK-MB in plasma were significantly increased,the concentrations of Fe^(2+)and MDA in PBMCs were increased,the expression of ACSL4 in PBMCs was up-regulated,and the activity of SOD was decreased,and the expression of GPX4 was down-regulated at T_(2-4) in two groups(P<0.05).Compared with C group,the plasma levels of NT-proBNP,cTnI and CK-MB were significantly decreased,the concentrations of Fe^(2+)and MDA in PBMCs were decreased,the expression of ACSL4 in PBMCs was down-regulated,the activity of SOD was increased,and the expression of GPX4 was up-regulated at T_(2-4) in UTI group(P<0.05).Conclusion The mechanism by which ulinastatin reduces perioperative myocardial injury may be related to inhibition of ferroptosis in PBMCs in the pediatric patients undergoing open heart surgery under CPB.
作者
鲁海兵
贾英萍
魏巍
周锐
齐金莲
Lu Haibing;Jia Yingping;Wei Wei;Zhou Rui;Qi Jinlian(Department of Anesthesiology,Children's Hospital Affiliated to Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou 450018,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2021年第12期1441-1445,共5页
Chinese Journal of Anesthesiology
基金
河南省科技攻关计划(182102310440)
河南省医学科技攻关计划(2018020611)。
关键词
胰蛋白酶抑制剂
心肺转流术
心肌损伤
单个核细胞
铁死亡
Trypsin inhibitor
Cardiopulmonary bypass
Myocardial injury
Mononuclear cells
Ferroptosis
