丹曲林对慢性心力衰竭大鼠心室细胞钙运转及心功能的影响

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摘要目的探讨丹曲林（DTL）对慢性心力衰竭（CHF）大鼠心室细胞钙运转及心功能的影响。方法将57只雄性SD大鼠按随机数字表法分为对照组、CHF组和干预组（n = 19），分别给予生理盐水、异丙肾上腺素（ISO）及ISO+DTL连续注射2周。干预2周后，行血流动力学和血清脑钠肽（BNP）水平检测。分离心室细胞，采用动缘探测系统记录心肌细胞收缩；心肌细胞钙荧光染料Fura-2 AM孵育后记录心室细胞钙瞬变（CaT），测量内质网钙容量（[Ca2+]SR）。Western blot检测心室Ryanodine 2型受体（RyR2）、内质网钙泵（SERC2a）及受磷蛋白（PLB）表达量。结果与对照组比较，CHF组左室舒张末期压力（LVEDP）、血清BNP水平、心室细胞舒张期Ca2+水平（[Ca2+]i）均显著升高（P < 0.01），CaT衰减时间、心室细胞收缩达峰时间（TP）及细胞舒张50%时间（TR50）均显著延长（P < 0.01），而左室收缩末期压力（LVESP）、心室收缩期压力上升及舒张期下降最大速度（±dP/dtmax）、心室细胞收缩百分比、CaT幅度、[Ca2+]SR、心室RyR2及SERCA2a表达量均显著降低（P < 0.01）。与CHF组比较，干预组LVEDP、血清BNP水平、[Ca2+]i均显著降低（P < 0.01），CaT衰减时间、TP及TR50均显著缩短（P < 0.01），而LVESP、±dP/dtmax、心室细胞收缩百分比、CaT幅度、[Ca2+]SR、心室RyR2及SERCA2a表达量均显著升高（P < 0.05或P < 0.01）。结论 DTL干预可改善CHF大鼠心功能，可能与DTL修复心室细胞钙运转有关。

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	胡冬冬刘韬石少波黄燕梁飒胡丹

关键词 ：心力衰竭, 丹曲林, 钙运转

Abstract：Objective To discuss the effects of Dantrolene (DTL) on calcium handling of ventricular myocytes and cardiac function in rats with chronic heart failure (CHF). Methods According to the random number table method, 57 adult male SD rats were assigned to control group, CHF group and intervention group (n = 19), which were given normal saline, Isoproterenol (ISO), and ISO+DTL, for 2 weeks. Two-week later, the hemodynamic parameters and serum B-type natriuretic peptide (BNP) level were measured. The ventricular myocytes were isolated, then the cell contractility was automatically detected by the video edge-detector system. The calcium transient (CaT） and sarcoplasmic reticulum (SR) calcium content ([Ca2+]SR) were recorded by loading cardiomyocytes with Fura-2 AM. The protein levels of ryanodine receptor 2 (RyR2), SR Ca2+-ATPase (SERCA2a) and phospholamban (PLB) were detected by Western blot. Results Compared with control group, left ventricular end diastolic pressure (LVEDP), serum BNP level, diastolic intracellular Ca2+ level ([Ca2+]i) were significantly increased in CHF group (P < 0.01), decay time constant (tau) of CaT, time to peak (TP) of cell contraction, time to 50% cell relaxation (TR50) were significantly extended in CHF group (P < 0.01), while left ventricular end systolic pressure (LVESP), ±dP/dtmax, cell shortening percentage, CaT amplitude, [Ca2+]SR, the protein levels of RyR2 and SERCA2a were significantly decreased in CHF group (P < 0.01). Compared with CHF group, LVEDP, serum BNP level, [Ca2+]i, decay time constant of CaT were significantly decreased in intervention group (P < 0.01), decay time constant of CaT, TP of cell contraction, TR50 were significantly shortened in intervention group (P < 0.01), whereas, LVESP, ±dP/dtmax, cell shortening percentage, CaT amplitude, [Ca2+]SR, the protein level of RyR2 and SERCA2a were markedly increased in intervention group (P < 0.05 or P < 0.01). Conclusion DTL treatment can improve cardiac function in rats with CHF, which may be related to the repair of calcium handling of ventricular myocytes by DTL.

Key words： Heart failure Dantrolene Calcium handling

基金资助:国家自然科学基金资助项目（81800337）；
湖北省自然科学基金青年项目（2018CFB418）。

通讯作者: 刘韬（1987.3-），男，博士；研究方向：心力衰竭。

引用本文:

胡冬冬刘韬石少波黄燕梁飒胡丹. 丹曲林对慢性心力衰竭大鼠心室细胞钙运转及心功能的影响[J]. 中国医药导报, 2020, 17(17): 4-8.
HU Dongdong LIU Tao SHI Shaobo HUANG Yan LIANG Sa HU Dan. Effects of Dantrolene on calcium handling of ventricular myocytes and cardiac function in rats with chronic heart failure. 中国医药导报, 2020, 17(17): 4-8.

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