Dan Q, Bai J, Cai Z, Lin K, Li Y
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.
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Sep 20;42(9):1359-1366. doi: 10.12122/j.issn.1673-4254.2022.09.12.
To investigate the changes in myocardial calcium currents in rats subjected to forced running exercise during acute hypoxia and their association with myocardial injury.
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 (PaO=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 Ca imaging was used to monitor intracellular Ca levels. The expressions of Cav1.2 channel and the cardiac ryanodine receptor (RyR2) were determined using Western blotting.
Compared with those in NQ group, the rats in HR group showed significantly decreased SOD activity ( < 0.01), increased h-FABP, hs-CRP and IMA levels ( < 0.05 or 0.01), obvious myocardial pathology, and prolonged APD50 and APD90 ( < 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 ( < 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 ( < 0.05 or 0.01).
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.
探讨急性缺氧时强迫跑步运动大鼠心肌钙电流的变化及其与心肌损伤的关系。
40只SD大鼠随机分为正常氧环境下的安静组和跑步组（分别为NQ组和NR组）以及急性缺氧环境下的安静组和跑步组（分别为HQ组和HR组）。通过将大鼠置于低压氧舱（PaO = 61.6kPa）每天4小时诱导缺氧；两个跑步组的大鼠每天被迫在跑轮上跑步4小时。采用酶消化法分离大鼠心室肌细胞，用膜片钳技术记录动作电位和电流，并用共聚焦钙成像监测细胞内钙水平。采用蛋白质免疫印迹法检测Cav1.2通道和心脏兰尼碱受体（RyR2）的表达。
与NQ组相比，HR组大鼠超氧化物歧化酶（SOD）活性显著降低（P < 0.01），心脏型脂肪酸结合蛋白（h-FABP）、超敏C反应蛋白（hs-CRP）和缺血修饰白蛋白（IMA）水平升高（P < 0.05或0.01），心肌病理改变明显，动作电位时程50%（APD50）和90%（APD90）延长（P < 0.05）。在不同应激条件下，急性缺氧时强迫跑步导致L型钙电流（ICa,L）密度增加最为显著，同时稳态激活曲线显著左移，稳态失活曲线显著右移。与NQ组相比，NR组、HQ组和HR组大鼠心肌细胞自发钙波事件发生率均较高，钙火花频率增加但幅度降低，心室肌细胞钙释放幅度增强，钙离子重吸收延迟；尤其是HR组这些变化最为明显（P < 0.05或0.01）。HR组Cav1.2通道和RyR2受体蛋白水平也显著升高（P < 0.05或0.01）。
急性缺氧时强迫跑步运动大鼠心肌损伤机制可能与氧化应激增加、钙电流增大及细胞内钙超载有关。
