Pravastatin Alleviates Intracellular Calcium Dysregulation Induced by Interleukin-6 via the Mitochondrial ROS Pathway in Adult Ventricular Myocytes
Pravastatin Alleviates Intracellular Calcium Dysregulation Induced by Interleukin-6 via the Mitochondrial ROS Pathway in Adult Ventricular Myocytes
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普伐他汀通过线粒体 ROS 途径减轻成人心室肌细胞中白细胞介素 6 诱导的细胞内钙失调
DOI：
10.1016/j.jphs.2020.01.013
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发表时间：
2020
影响因子：
3.5
通讯作者：
Changsheng Ma
中科院分区：
文献类型：
--
作者：
Song Zuo;Linling Li;Le Jiang;Chao Jiang;Xin Li;Songnan Li;Songnan Wen;Rong Bai;Xin Du;Jianzeng Dong;Nian Liu;Yanfei Ruan;Changsheng Ma
急性炎症常导致心肌细胞心律失常的增加。我们研究了普伐他汀对分离心室肌细胞急性给药促炎细胞因子引起的钙障碍的保护作用及其潜在机制。野生型小鼠腹腔注射普伐他汀20 mg/kg /天或等量生理盐水5天。通过Ionoptix和共聚焦显微镜研究了急性暴露于白细胞介素-6 (IL-6) (1 ng/ml) 120分钟后新鲜分离的心室肌细胞的细胞质Ca2+处理。急性给予临床相关浓度的IL-6干扰了心室肌细胞对钙的处理，表现为振幅降低，Ca2+瞬态衰减时间延长，肌浆网（SR）钙储存减少。自发Ca2+释放的频率，包括钙火花和自发钙波，在IL-6的设置显著增强。值得注意的是，普伐他汀预处理可以缓解Ca2+循环紊乱，减少由IL-6引起的自发Ca2+泄漏。线粒体ROS通路可能是普伐他汀保护作用的潜在机制。普伐他汀通过线粒体ROS途径保护心肌细胞免受IL-6诱导的钙障碍，这表明普伐他汀可能是急性炎症下心脏损伤的一种有希望的辅助治疗策略。
Acute inflammation often contributes to the increased arrhythmogenesis in the cardiomyocytes. We investigated the protective effects of pravastatin on calcium disorders induced by acute administration of pro-inflammatory cytokines in isolated ventricular myocytes and its underlying mechanisms. Wild-type mice were intraperitoneally injected for five days with either pravastatin 20 mg/kg per day or an equal volume of normal saline. Cytosol Ca2+handling was studied in freshly isolated ventricular myocytes after acute exposure of interleukin-6 (IL-6) (1 ng/ml) for 120 min by Ionoptix and confocal microscopy. Acute administration of clinically relevant concentrations of IL-6 disturbed calcium handling in ventricular myocytes, which presented as decreased amplitudes, prolonged decay times of Ca2+transients, and reduced sarcoplasmic reticulum (SR) calcium stores. The frequency of spontaneous Ca2+release, including calcium sparks and spontaneous calcium waves, was dramatically enhanced in the setting of IL-6. Notably, the pretreatment of pravastatin alleviated disturbed Ca2+cycling, reduced spontaneous Ca2+leakage induced by IL-6. Mitochondrial ROS pathway may constitute the underlying mechanism of the protective effects of pravastatin. Pravastatin protected the cardiomyocytes against calcium disorders induced by IL-6 via the mitochondrial ROS pathway, which suggests that pravastatin may represent a promising auxiliary therapeutic strategy for cardiac injury under acute inflammation.