不同氧亲和力血红蛋白类氧载体对大鼠离体心脏的保护作用研究  

Protective effect of hemoglobin oxygen carrier with different oxygen affinity on isolated rat hearts

作　　者：周文涛 李燊 郝莎莎 张鸿辉 王红 刘嘉馨 杨成民 ZHOU Wentao;LI Shen;HAO Shasha;ZHANG Honghui;WANG Hong;LIU Jiaxin;YANG Chengmin(Institute of Blood Transfusion,Chinese Academy of Medical Sciences,Chengdu 610052,China)

机构地区：[1]中国医学科学院输血研究所,四川成都610052

出　　处：《中国输血杂志》2021年第3期214-218,共5页Chinese Journal of Blood Transfusion

基　　金：中国医学科学院医学与健康科技创新工程(2016-I2M-1-018、2017-I2M-3-021);协和青年科研基金(2017310037)。

摘　　要：目的探讨不同氧亲和力的血红蛋白类氧载体(HBOCs)对大鼠离体心脏的保护作用。方法采用Langendorff离体心脏灌注模型,按30 min KH液基线灌注45只成年雄性SD大鼠(SPF级)——随机均分入假手术组、对照组:St.Thomas(STS)液灌注量3 mL/100 g体重;高P50 HBOCs组:[STS液+高P50 HBOCs(P50=35.0 mmHg, 2.5 mg/100 g)制品]灌注量为3 mL/100 g体重;中P50 HBOCs组:[STS液+中P50 HBOCs(P50=26.5.0 mmHg, 2.5 mg/100 g)制品]灌注量为3 mL/100 g体重;低P50 HBOCs组:[STS液+低P50 HBOCs(P50=11.0 mmHg, 2.5 mg/100 g)制品]灌注量为3 mL/100 g体重——心脏停跳即置于37oC水浴使心脏缺血35 min后,复灌2 h。观察记录复灌过程中大鼠心脏左室发展压(LVDevP)、左室舒张末压(LVEDP)、左室压力的变化率(LVPCR)和心率(HR),并将分别取自各组只大鼠基础和再灌注阶段1 min灌流液,用血气分析仪测定大鼠血气指标,并采用ELISA试剂盒测定心肌损伤标志酶[心肌酶肌酸激酶(CK-MB)、乳酸脱氢酶(LDH)和α-羟基丁酸脱氢酶(α-HBDH)]的释放情况。结果 5组大鼠在心脏基础灌注阶段的心功能及心肌酶释放量相近(P>0.05);但到了复灌阶段,除HR变化不明显(P>0.05)外,高、中、低3个P50 HBOCs组与对照组大鼠心脏的LVDevP(mmHg)为10.69±3.65 vs 8.50±2.88、23.26±5.62 vs 8.50±2.88、35.60±3.82 vs 8.50±2.88, LVEDP(mmHg)为43.34±8.08 vs 54.64±7.42、39.43±8.30 vs 54.64±7.42、31.46±4.11 vs 54.64±7.42,dp/dt为12.09±9.96 vs 6.09±0.98、25.65±8.87 vs 6.09±0.98、35.32±9.33 vs 6.09±0.98,-dp/dt为17.53±11.28 vs 11.39±2.16、28.80±13.70 vs 11.39±2.16、43.36±3.83 vs 11.39±2.16(均为P<0.05);3个P50 HBOCs组复跳情况以及CK-MB、LDH、α-HBDH的释放量都快优于对照组(P<0.05)。3个P50 HBOCs组中,以低P50 HBOCs组大鼠的各项心功能指标最优,高、中、低HBOCs组的心肌酶指标分别为CK-MB(ng/mL):110.47±4.04、90.20±2.46、77.10±3.51;LDH(U/L):162.23±7.71、135.13±23.69、92.20±4.21;a-HBDH(U/L):228.00±8.03、17Objective To explore the protective effects of hemoglobin base on oxygen carries(HBOCs) with different oxygen affinity on isolated rat hearts. Methods Using Langendorff isolated heart perfusion model, 45 adult male SD rats(SPF grade), perfused with 30 min KH solution baseline, were randomly divided into sham operation group and control group: St. Thomas(STS) solution perfusion volume was 3 mL/100 g body weight;high P50 HBOCs group: [STS + high P50 HBOCs(P50=35.0 mmHg, 2.5 mg/100 g) product] perfusion volume was 3 mL/100 g body weight;medium P50 HBOCs group: [STS + medium P50 HBOCs(P50=26.5.0 mmHg, 2.5 mg/100 g) product] perfusion volume was 3 mL/100 g body weight;low P50 HBOCs group: [STS + low P50 HBOCs(P50=11.0 mmHg, 2.5 mg/100 g) product] perfusion volume was 3 mL/100 g body weight, and the heart was arrested and placed in a 37℃ water bath to make the heart ischemic for 35 minutes, and then reperfused for 2 hours. The left ventricular development pressure(LVDevP), left ventricular end diastolic pressure(LVEDP), the rate of change of left ventricular pressure(LVPCR) and heart rate(HR) in the rat heart during reperfusion were observed and recorded. 1 min perfusion fluid from each rat in the basic and reperfusion phase was taken, and blood gas analyzer was used to measure the blood gas indexes of rats, and the myocardial injury marker enzymes [cardiac enzyme creatine kinase(CK-MB), lactate dehydrogenase(LDH) and the release of α-hydroxybutyrate dehydrogenase(α-HBDH)] were measured by ELISA kit. Results The cardiac function and the release of myocardial enzymes in the 5 groups of rats in the basal cardiac perfusion stage were similar(P>0.05). However, in the reperfusion stage, except for the insignificant changes in HR(P>0.05), the heart LVDevP(mmHg) of the three P50 HBOCs groups and the control group were 10.69±3.65 vs 8.50±2.88, 23.26 ±5.62 vs 8.50±2.88, 35.60±3.82 vs 8.50±2.88, LVEDP(mmHg) were 43.34±8.08 vs 54.64±7.42, 39.43±8.30 vs 54.64±7.42, 31.46±4.11 vs 54.64±7.42, dp/dt were 12.09±9.96 v

关 键 词：血红蛋白氧载体 离体心脏 体外循环 氧分压 50%血氧饱和度 心脏保护 心功酶 动物实验 大鼠 

分 类 号：R457.1[医药卫生—治疗学] R654.1[医药卫生—临床医学]