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首页> 外文期刊>Cardiovascular therapeutics >Taxol, a microtubule stabilizer, improves cardiac functional recovery during postischemic reperfusion in rat in vitro
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Taxol, a microtubule stabilizer, improves cardiac functional recovery during postischemic reperfusion in rat in vitro

机译：紫杉醇，一种微管稳定剂，可改善大鼠缺血再灌注后的心脏功能恢复

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Aims: Microtubule disruption contributes to cellular and organic dysfunction, and is implicated in ischemia/reperfusion (I/R) injury. The purpose of this study was to explore the effects of taxol, a microtubule stabilizer, on cardiac functional recovery during reperfusion. Methods: Left ventricular developed pressure, left ventricular end-diastolic pressure, maximal time derivatives of pressure and the severity of ventricular arrhythmias were analyzed in isolated rat heart. Microtubule structure was immunohistochemically measured. Apoptosis and necrosis was identified with TUNEL or TTC staining, respectively. Mitochondrial permeability transition pore (mPTP) mRNA expression was examined by real-time polymerase chain reactions. mPTP opening, reactive oxygen species (ROS), and oxidative enzyme activities were measured with fluorometric or spectrophotometric techniques. Intracellular calcium concentration ([Ca 2+] i) and Ca 2+ transients were examined by Fura-2-AM and Fluo-3-AM, respectively. Cytosolic cytochrome c, sarcoplasmic reticulum Ca 2+-ATPase (SERCA2), ryanodine receptors (RyR), phospholamban (PLB), and PLB phosphorylation were analyzed by Western blot. Effective refractory period (ERP) and afterpotential-mediated activity were detected using microelectrode. Results: Taxol improved the functional recovery of post-I/R. Taxol preserved the intact microtubule structure in reperfusion. mPTP mRNA expression was unchanged while the mPTP opening was reduced by taxol, and this effect was accompanied by the decreased ROS level caused by oxidative enzymes activities' changes. Taxol reduced apoptosis and the level of cytosolic cytochrome c in reperfusion. Taxol also promoted rapid recovery of [Ca 2+] i, prevented reduction of the amplitude of Ca 2+ transients and shortened the decay time of Ca 2+ transients. The protein expression of SERCA2, RyR, and PLB remained unchanged in reperfusion. Taxol prevented the increase of Phospho-Thr17-PLB and Phospho-Ser16-PLB in reperfusion. In addition, taxol facilitated rapid recovery of ERP and counter-acted afterpotential-mediated activity. Conclusion: Taxol may effectively improve cardiac functional recovery during reperfusion via inhibiting mPTP opening, ameliorating abnormal calcium homeostasis, and reducing the substrates associated with arrhythmias.
机译：目的：微管破坏导致细胞和器质性功能障碍，并涉及缺血/再灌注（I / R）损伤。这项研究的目的是探讨紫杉醇，一种微管稳定剂，对再灌注期间心脏功能恢复的影响。方法：分析离体大鼠心脏的左心室发育压力，左心室舒张末期压力，最大时间导数和心律失常的严重程度。用免疫组织化学方法测定微管结构。通过TUNEL或TTC染色分别鉴定凋亡和坏死。通过实时聚合酶链反应检查线粒体通透性转换孔（mPTP）mRNA的表达。用荧光法或分光光度法测量了mPTP的开放度，活性氧（ROS）和氧化酶的活性。通过Fura-2-AM和Fluo-3-AM分别检测细胞内钙浓度（[Ca 2+] i）和Ca 2+瞬变。通过Western印迹分析细胞质细胞色素c，肌质网Ca 2 + -ATPase（SERCA2），ryanodine受体（RyR），phospholamban（PLB）和PLB磷酸化。使用微电极检测有效不应期（ERP）和后电位介导的活性。结果：紫杉醇改善了I / R后的功能恢复。紫杉醇在再灌注中保留了完整的微管结构。紫杉醇可降低mPTP的开放性，而mPTP mRNA的表达则保持不变，并且这种作用伴随着氧化酶活性的变化而导致ROS水平降低。紫杉醇减少再灌注中的细胞凋亡和细胞溶质细胞色素c的水平。紫杉醇还促进了[Ca 2+] i的快速恢复，防止了Ca 2+瞬变幅度的减小，并缩短了Ca 2+瞬变的衰减时间。 SERCA2，RyR和PLB的蛋白表达在再灌注过程中保持不变。紫杉醇阻止了再灌注中Phospho-Thr17-PLB和Phospho-Ser16-PLB的增加。此外，紫杉醇促进了ERP的快速恢复并抵消了后电位介导的活性。结论：紫杉醇可通过抑制mPTP的开放，改善异常的钙动态平衡并减少与心律不齐相关的底物，从而有效改善再灌注过程中的心脏功能恢复。

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