南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (9): 1359-1366.doi: 10.12122/j.issn.1673-4254.2022.09.12

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急性低氧跑大鼠的心肌损伤与心肌钙电流的变化有关

但 晴，白 婧，蔡钟奇，林 琨，李 泱   

  1. 解放军总医院第一医学中心心血管内科，北京 100039；郑州大学第一附属医院心血管内科，河南 郑州 450052；中国人民解放军南部战区总医院干部病房，广东 广州 510014；解放军总医院第六医学中心心血管病医学部，北京 100048
  • 发布日期:2022-09-28

Changes of myocardial calcium currents in rats with myocardial injury induced by running exercise during acute hypoxia

DAN Qing, BAI Jing, CAI Zhongqi, LIN Kun, LI Yang   

  1. Department of Cardiology, Fist Medical Center, Chinese PLA General Hospital, Beijing 100000, China; Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China; Cadre's Ward, General Hospital of Southern Theater Command of PLA, Guangzhou 510000, China; Department of Cardiology, Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
  • Published:2022-09-28

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摘要： 目的 探讨钙离子在急性低氧跑大鼠心肌损伤中的作用。方法 将40只大鼠随机分为常氧安静组（NQ）、常氧跑步组（NR）、低氧安静组（HQ）和低氧跑步组（HR），10只/组。两个低氧组每天在低压氧舱（氧分压61.6 kPa）4 h，两个运动组每天使用跑轮装置运动4 h，其中低氧跑步组在低压氧舱运动4 h。使用酶消化法分离大鼠心室肌细胞，膜片钳技术记录动作电位和电流，共聚焦钙离子成像技术检测细胞内钙离子水平，Western blotting分析该蛋白的表达。结果 与NQ组相比，HR组SOD显著降低，h-FABP显著升高（P<0.01）。HR组hs-CRP和IMA均高于NQ组（P<0.05或P<0.01）。HR组心肌纤维呈波浪形，横带增厚，部分细胞核浓缩。HR组APD50、APD90明显延长（P<0.05）。在不同的应激条件下，ICa，L电流密度均有不同程度的增加。其中，HR组的增加最为显著。HR组稳态激活曲线显著左移，稳态失活曲线显著右移。NR组、HQ组和HR组的自发性钙波事件均高于NQ组，尤其是HR组（P<0.05或P<0.01）。应激3组大鼠心肌细胞钙火花频率增加，火花幅度降低，其中HR组变化最显著。此外，与NQ组相比，应激组心室肌细胞钙释放幅度降低，钙离子回流吸收延迟。HR组Cav1.2通道和RyR2受体蛋白水平明显升高（P<0.05或P<0.01）。结论 急性低氧运动大鼠心肌功能损害的机制与钙电流增加和细胞内钙超载有关。

关键词: 急性低氧跑；大鼠；心室肌细胞；L型钙电流；细胞内钙

Abstract: Objective To investigate the changes in myocardial calcium currents in rats subjected to forced running exercise during acute hypoxia and their association with myocardial injury. Methods Forty SD rats were randomized into quiescent group and running group either in normal oxygen (NQ and NR groups, respectively) or in acute hypoxia (HQ and HR groups, respectively). Hypoxia was induced by keeping the rats in a hypobaric oxygen chamber (PaO2=61.6kpa) for 4 h a day; the rats in the two running groups were forced to run on running wheels for 4 h each day. Rat ventricular myocytes was isolated by enzymatic digestion for recording action potentials and currents using patch clamp technique, and confocal Ca2 + imaging was used to monitor intracellular Ca2 + levels. The expressions of Cav1.2 channel and the cardiac ryanodine receptor (RyR2) were determined using Western blotting. Results Compared with those in NQ group, the rats in HR group showed significantly decreased SOD activity (P<0.01), increased h-FABP, hs-CRP and IMA levels (P<0.05 or 0.01), obvious myocardial pathology, and prolonged APD50 and APD90 (P<0.05). Of the different stress conditions, forced running in acute hypoxia resulted in the most prominent increase of the densities of ICa,L currents, causing also a significant left shift of the steady state activation curve and a significant right shift of the steady state inactivation curve. Compared with those in NQ group, the rats in NR, HQ and HR groups all exhibited higher rates of spontaneous calcium wave events in the cardiac myocytes, increased frequency of calcium sparks with lowered amplitude, enhanced calcium release amplitude in the ventricular myocytes, and delayed calcium ion reabsorption; in particular, these changes were the most conspicuous in HR group (P<0.05 or 0.01). There was also a significant increase in the protein levels of Cav1.2 channel and RyR2 receptor in HR group (P<0.05 or 0.01). Conclusions The mechanism of myocardial injury in rats subjected to forced running in acute hypoxia may involve the increase of oxidative stress and calcium current and intracellular calcium overload.

Key words: running during acute hypoxia; rats; ventricular myocytes; L-type calcium current; intracellular calcium