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《国际心血管病杂志》[ISSN:1006-6977/CN:61-1281/TN]

期数:

2020年02期

页码:

97-102

栏目:

基础研究

出版日期:

2020-03-29

文章信息/Info

Title:

Chronic hypoxia increases myocardial tolerance to acute ischemic reperfusion injury

作者:

贾维坤 马瑞东 曾小飞 姚益

610500 成都医学院第一附属医院胸心外科

Author(s):

JIA Weikun;  MA Ruidong;  ZENG Xiaofei;  YAO Yi

Department of Thoracic Surgery, The First Affiliated Hospital of Chendu Medical College, Sichuan 610500, China

关键词:

缺氧;  心肌缺血;  再灌注损伤

Keywords:

Hypoxia;  Myocardial ischemic;  Reperfusion injury

分类号:

-

DOI:

10.3969/j.issn.1673-6583.2020.02.009

文献标识码:

-

摘要:

目的:探讨慢性缺氧对心肌耐受急性缺血再灌注损伤的影响。方法:将SD大鼠随机分为在体实验组、在体对照组、离体实验组、离体对照组。在体及离体实验组大鼠在模拟海拔5 000 m的动物低压低氧舱中生活,舱内条件:大气压54 kPa、氧分压11.33 kPa、温度25 ℃; 在体及离体对照组大鼠在正常氧环境中喂养。分别通过结扎左冠状动脉前降支或Langendorff离体心脏灌流系统建立在体及离体心肌缺血再灌注模型,检测4组大鼠再灌注损伤前后心功能指标、心肌梗死面积和心肌酶变化。结果:在体实验可见,在体实验组缺血再灌注前心率(HR)、左室收缩末期容积(LVESV)均明显大于在体对照组,舒张期室间隔厚度(IVSd)、收缩期室间隔厚度(IVSs)、舒张期左室后壁厚度(LVPWd)、收缩期左室后壁厚度(LVPWs)、左室射血分数(LVEF)、左室缩短分数(LVFS)、左室舒张末期容积(LVEDV)、每搏输出量(SV)均明显小于在体对照组(P均<0.05); 缺血再灌注后,在体实验组HR、IVSs、LVPWd、LVPWs、LVEF、LVFS均明显大于在体对照组,IVSd、LVEDV、LVESV、SV均明显小于在体对照组(P均<0.05); 缺血再灌注可使在体实验组、在体对照组的心功能出现不同程度的损伤,而对在体对照组的损伤更明显; 再灌注损伤后,在体实验组心肌梗死面积明显小于在体对照组,肌酸激酶同工酶(CK-MB)活性明显低于在体对照组(P均<0.05),两组乳酸脱氢酶(LDH)活性的差异无统计学意义。离体实验可见,缺血再灌注损伤前离体实验组左室发展压(LVDP)、max(dp/dt)、min(dp/dt)均明显低于离体对照组(P均<0.05),两组左室舒张末期压力(LVEDP)的差异无统计学意义; 缺血再灌注损伤后离体实验组LVDP、max(dp/dt)、min(dp/dt)均明显高于离体对照组,LVEDP明显低于离体对照组(P均<0.05); 再灌注损伤后离体实验组心肌梗死面积明显小于离体对照组,LDH活性明显高于离体实验组(P均<0.05)。结论:慢性缺氧可提升心肌耐受急性缺血再灌注损伤的能力。

Abstract:

Objective:To study the effects of chronic hypoxia on myocardial tolerance to acute ischemic reperfusion injury.Methods:Sprague-Dawley rats were divided into four groups, namely in vivo experimental group, in vivo control group, in vitro experimental group, and in vitro control group. The rats in vivo experimental group and in vitro experimental group lived in a low-pressure hypoxic chamber simulating the environment in an altitude of 5 000 meters. The conditions was set as follow: atmospheric pressure 54 kPa, oxygen partial pressure 11.33 kPa, temperature 25 ℃. The rats in vivo control group and in vitro control group were fed under normal oxygen conditions. In vivo and in vitro myocardial ischemia and reperfusion models were established by ligating the anterior descending branch of left coronary artery and using Langendorff's isolated cardiac perfusion system, respectively. Ventricular function indexes, myocardial infarction area and myocardial enzyme level before and after reperfusion injury were detected in the four groups.Results:The heart rate(HR)and left ventricular end-systolic volume(LVESV)in the in vivo experimental group before ischemia-reperfusion were significantly larger than those in the vivo control group(all P<0.05), while interventricular septal thickness at diastole(IVSd), interventricular septal thickness at systolic(IVSs), left ventricular posterior wall of diastolic(LVPWd), left ventricular systolic posterior wall thickness(LVPWs), left ventricular ejection fraction(LVEF), left ventricular short axis shortening rate(LVFS), left ventricular end-diastolic volume(LVEDV)and stroke volume(SV)were significantly smaller than those in vivo control group(all P<0.05). After ischemia-reperfusion, the HR, IVSs, LVPWd, LVPWs, LVEF, and LVFS in the experimental group were significantly larger than those in the vivo control group(all P<0.05), and IVSd, LVEDV, LVESV, and SV were smaller than those in the vivo control group(all P<0.05). After ischemia-reperfusion, the cardiac function of the in vivo experimental group and the in vivo control group were damaged to defferent degrees, especially in the in vivo control group. Campared with the in vivo control group, the myocardial infarction area was smaller with lower activity of creatine kinase isoenzyme(CK-MB )in the in vivo experimental group(all P<0.05). There was no statistical difference as for the lactate dehydrogenase(LDH)activity between the two groups(P>0.05). In the vitro experiment group, the left ventricular developed pressure(LVDP), maximum pressure rise rate in left ventricular(max dp/dt)and pressure maximum decline rate in left ventricular(min dp/dt)before ischemia-reperfusion injury were lower than those of the control group(all P<0.05), and there was no significant difference in LVEDP(P>0.05). After ischemia-reperfusion injury, the LVDP, max dp/dt, and min dp/dt in the experimental group were significantly higher than those in the control group, and LVEDP was significantly lower than that in the control group.The myocardial infarct size of the experimental group was smaller than that of the vitro control group after reperfusion injury(all P<0.05). Campared with the control group, the myocardial infarction area was smaller with lower LDH activity in the experimental group after reperfusion injury(all P<0.05).Conclusions:Chronic hypoxia can improve myocardial tolerance to acute ischemia-reperfusion injury.

参考文献/References

[ 1 ] 翟恒博. 缺血性心脏病再认识[J]. 心血管病学进展, 2016, 37(4):395-400.
[ 2 ] Weiwei C, Runlin G, Lisheng L, et al. Outline of the report on cardiovascular diseases in China, 2014[J]. Eur Heart J Suppl, 2016, 18(Suppl F):F2-F11.
[ 3 ] 姚尖平, 张希, 徐颖琦, 等. 低氧分压控制性再灌注与紫绀缺氧未成熟心肌保护[J]. 中华胸心血管外科杂志, 2003, 19(5):46-49.
[ 4 ] Yang J, Yin HS, Cao YJ, et al. Arctigenin attenuates ischemia/reperfusion induced ventricular arrhythmias by decreasing oxidative stress in rats[J]. Cell Physiol Biochem, 2018, 49(2):728-742.
[ 5 ] 陈昱, 明腾. 心肌缺血再灌注损伤机制的研究进展[J]. 山东医药, 2014, 41(54):98-100.
[ 6 ] Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium[J]. Circulation, 1986, 74(5):1124-1136.
[ 7 ] Kolár F, Ostádal B. Molecular mechanisms of cardiac protection by adaptation to chronic hypoxia[J]. Physiol Res, 2004, 53(Suppl 1):S3-S13.
[ 8 ] Tepp K, Puurand M, Timohhina N, et al. Changes in the mitochondrial function and in the efficiency of energy transfer pathways during cardiomyocyte aging[J]. Mol Cell Biochem, 2017, 432(1/2):141-158.
[ 9 ] Lee SH, Wolf PL, Escudero R, et al. Early expression of angiogenesis factors in acute myocardial ischemia and infarction[J]. N Engl J Med, 2000, 342(9):626-633.
[10] 周胜凯, 秦川, 陈林, 等. EPO对慢性缺氧心肌细胞线粒体生物合成的影响[J]. 第三军医大学学报, 2013, 35(12):1192-1196.
[11] 肖颖彬, 蹇朝. 心肌慢性缺氧适应的研究进展[J]. 西部医学, 2015, 27(3):321-322.
[12] Peng X, Shao J, Shen Y, et al. FAT10 protects cardiac myocytes against apoptosis[J]. J Mol Cell Cardiol, 2013, 59:1-10.
[13] 黄静兰, 康冰瑶, 屈艺, 等. 外泌体对缺血再灌注器官损伤的保护作用[J]. 中国修复重建外科杂志, 2017, 31(6):751-754.
[14] Song E, Ramos SV, Huang X, et al. Holo-lipocalin-2-derived siderophores increase mitochondrial ROS and impair oxidative phosphorylation in rat cardiomyocytes[J]. Proc Natl Acad Sci U S A, 2018, 115(7):1576-1581.
[15] Hausenloy DJ, Yellon DM. Targeting myocardial reperfusion injury—the search continues[J]. N Engl J Med, 2015, 373(11):1073-1075.
[16] 陈效安, 胡孟芬, 宋达琳. 心肌缺血再灌注损伤与心肌保护[J]. 中国医刊, 2016, 51(11):23-26.
[17] 伍宁, 齐丹, 曲爱娟. 低氧诱导因子1在心肌缺血-再灌注损伤中的作用及机制研究进展[J]. 生理科学进展, 2017, 5(5):347-351.
[18] 国科, 刘达兴, 容松. 心肌缺血再灌注损伤的发生机制及其防治策略[J]. 中国医药导报, 2016, 13(29):37-40.
[19] Tverskaya MS, Gankovskaya LV, Sukhoparova VV, et al. Effect of natural cytokine complex on the structure and metabolism of the cardiac conduction system in the myocardium under normally and increased hemodynamic load[J]. Bull Exp Biol Med, 2018, 164(6):716-720.
[20] Sano HI, Toki T, Naito Y, et al. Developmental changes in the balance of glycolytic ATP production and oxidative phosphorylation in ventricular cells: a simulation study[J]. J Theor Biol, 2017, 419:269-277.

备注/Memo

备注/Memo:

基金项目: 四川省教育厅重点项目(17ZA0123)
作者单位: 610500 成都医学院第一附属医院胸心外科
通信作者: 贾维坤,E-mail: wk_jia315@163.com

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更新日期/Last Update: 2020-03-30